Pediatric reference ranges

54 Reference intervals and orienting ranges for Clinical Chemistry and Laboratory Medicine in fetuses, newborn and adolescents

D. Klarmann, G. Hintereder, L. Thomas

The reference intervals, orienting ranges and decision limits of laboratory investigations provide physicians with objective data for clinical interpretation of a laboratory result. The combination of presumptive diagnosis with the reference interval based laboratory test result are fundamental for accurate diagnosis and differentiation of medical disorders. The directive 98/79 CE of the European community was imposed on the manufacturers of the diagnostic in vitro industry to provide reference intervals of laboratory reagent kits on the package insert in 1998 /1, 2/. Many international organisations recommended providing such information. In 2005, a joint meeting gathered the Committee on Reference Limits and Decision Limits of the International Federation of Clinical Chemistry (IFCC). It was decided to revise the original document on the determination of reference values published in 1995 by the National Committee for Clinical Laboratory Standards (NCCLS). Finally, the working group was set up with members designated by the Clinical Laboratory Standard Institute (CLSI). The goal of the joint committee was to revise former documents. The updated document was published in 2008 under the guarantee of the IFCC and CSLI and was entitled “Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline – Third Edition – C28-A3“ /3/.

In the document of the IFCC, statistical methods for the determination of reference limits and reference intervals were determined /1/:

The parametric method assumes that the observed values follow a Gaussian probability curve. This implies in practice that for many analytes not following the Gaussian form, the data must be transformed (normalisation).
The non-parametric method makes no specific assumptions about the mathematical form of the probability distribution of the observed reference values. The recommended statistical methodology is the non-parametric method which does not require special competence in statistics, but a minimum of 120 reference individuals is recognised by the IFCC as a good compromise /2/.
The robust method: This method is a compromise between the parametric and the non-parametric methods. It reqiures neither a large number of observations nor a Gaussian distribution. Instead, the mean and standard deviation, robust method measures location and spread.

Reference intervals may be replaced by decision limits for differentiation of healthy and sick, e.g., LDL-cholesterol, glycated hemoglobin. Continuous reference intervals from birth to adulthood are not available for most laboratory analytes because of ethical and practical constraints of defining reference intervals using a population of healthy community children. Because access to blood samples from healthy children is limited by ethical and practical constraints. Newborn and infant children are most affected by these restrictions /4/.

The following efforts have been made to resolve these issues:

KiGGS – The German survey on children’s health as data base for reference intervals. Continuous reference intervals are reported for 28 analytes on the basis of a representative German cohort of 14,255 children aged 1.5 to 18 years /5/.
Reference intervals were calculated from a laboratory database containing a mixture of healthy and pathologic samples; the distribution of supposedly healthy samples was estimated from the whole data set with a statistical approach and used to calculate continuous reference intervals /6/. A comparison of the indirect method for determination of generated reference intervals to results from KIGGS and CALIPER showed consistent upper and lower reference limits and onset of age-dependent changes /6/. Another study /7/ provided qualitative and quantitative measures for the extent to which results for individual children can or can not be compared across analyzer types, and the feasibility for reference interval harmonization.
The Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) provides sex-specific reference intervals from birth to adulthood for 100 biomarkers. CALIPER has created a biobank of healthy pediatric samples from over 9,700 community children and adolescents of the greater Toronto and Hamilton areas from 1 to 19 years of age. The majority of CALIPER reference intervals originally established on Abbott assays have been transferred to assays from other manufacturers including Beckman Coulter, Ortho, Roche, and Siemens /8/. Reference intervals of CALIPER are freely available and are used from laboratories in the USA, Canada and Europe. In CALIPER studies the healthy population consisted of Canadian children. However, concerns related to the population is warranted. In comparison children in Canada, European children have different nutrition (e.g., supply of iodine and vitamins ) and lifestile. Therefore reference ranges of Canadian children are not always comparable with reference ranges of European children. There is no information of fetal, premature babies and newborn reference ranges in the CALIBER studies.

In addition to Tables 54-1 to 54-3 further important reference ranges are given in the literature:

Hematologic reference ranges in premature babies. Refer to Ref. /9/
Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Refer to Ref. /10/.

Representations of the reference intervals are provided in Tables 54-1, 54-2, 54-3 and 54-4. The protocol for obtaining reference values and determining reference intervals was not complied with in all studies. With exception of the KIGGS study /5, 16/ no reference ranges according to the recommendations of IFFC are shown. Tables 54-1 to 54-4 show essentially orientational ranges, because important recommendations (patient number, methodology according to CSLI Document C28-3) were not taken into account /4/.

Reference intervals and results of immunoassays of different manufacturers cannot be compared. The authors recommend searching Caliper Pediatric Reference Interval Database for pediatric reference intervals for immunoassay analyzers:

Abbott; refer to references /42/ and /43/
Beckman Coulter; refer to reference /44/
Ortho; refer to reference /45/
Roche; refer to references /46/ and /47/
Siemens; refer to reference /48/.

Table 54-1 Reference intervals and orienting ranges of “normal” for clinical chemistry analytes

Tests	Age (d, days; m, months; y, years)	Sex (M, male; F, female)	Reference interval	Median	Comment
25-0H vitamin D ug/L (nmol/L)	1.5–2 y	M	9.2–51.6 (23–129)	27.2 (68)	Children ≥ 1.5 y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Dia Sorin chemiluminescence immunoassay. Samples of children (M = 5108; F = 4908) of representative locations all over Germany were selected. Lit. /5/
	1.5–2 y	F	7.6–49.6 (19–124)	25.6 (64)
	2.5–3 y	M	6.8–46.0 (17–115)	24.8 (62)
	2.5–3 y	F	6.8–43.2 (17–108)	21.6 (54)
	4–6 y	M	4.8–41.2 (12–103)	18.0 (45)
	4–6 y	F	5.2–39.2 (13–98)	17.6 (44)
	7–9 y	M	4.4–39.2 (11–98)	17.2 (43)
	7–9 y	F	4.8–36.0 (12–90)	16.4 (41)
	10–13 y	M	4.8–36.8 (12–92)	16.8 (42)
	10–13 y	F	4.0–33.6 (10–84)	19.6 (49)
	14–17 y	M	4.0–40.8 (10–102)	14.8 (37)
	14–17 y	F	3.6–48.0 (9–120)	16.4 (41)
Alkaline phosphatase U/l (ukatal/L)	1–7 d	M+F	< 357 (< 5.96)		d: The ranges are presented. Laboratory investigations were carried out using Dade Behring Dimension RXL. About 60 outpatient and inpatient children were examined. Lit. /11/ y: Interval of 2.5% and 97.5% percentiles. Determination at 37 °C according to IFCC. Samples of 75–142 outpatient and inpatient children were examined. Lit. /12/
	0–1 y	M+F	89–370 (1.49–6.2)
	> 1–3 y	M+F	91–334 (1.52–5.6)
	4–6 y	M+F	97–316 (1.61–5.3)
	7–12 y	M	110–316 (1.83–5.3)
	7–12 y	F	120–340 (2.00–5.7)
	13–17 y	M	75–363 (1.25–6.1)
	13–17 y	F	49–328 (0.82–5.5)
ALT (GPT) U/L (ukatal/L)	1–7 d	M+F	< 54.0 (< 0.90)		d: The ranges are presented. Laboratory investigations were carried out using Dade Behring Dimension RXL. About 60 outpatient and inpatient children were examined. Lit. /11/ y: Interval of 3% and 97% percentiles. Determination with pyridoxal phosphate at 37 °C according to IFCC. Samples of 75–206 outpatient and inpatient children were examined. Lit. /12/
	0–1 y	M+F	4.2–49.2 (0.07–0.82)
	> 1–3 y	M+F	6.6–29.4 (0.11–0.49)
	4–6 y	M+F	4.8–39.0 (0.08–0.65)
	7–12 y	M+F	7.2–43.8 (0.12–0.73)
	13–17 y	M+F	7.8–45.0 (0.13–0.75)
AST (GOT) U/l (ukatal/L)	1–7 d	M+F	< 96 (< 1.60)		d: The ranges are presented. Laboratory investigations were carried out using Dade Behring Dimension RXL. About 60 outpatient and inpatient children were examined. Lit. /11/ y: Interval of 3% and 97% percentiles. Determination with pyridoxal phosphate at 37 °C according to IFCC. Samples 76–209 outpatient and inpatient children were examined. Lit. /12/
	0–1 y	M+F	14.4–77 (0.24–1.29)
	> 1–3 y	M+F	19.3–71 (0.32–1.19)
	4–6 y	M+F	15.0–53 (0.25–0.89)
	7–12 y	M+F	18.6–48 (0.31–0.80)
	13–17 y	M+F	15.0–41.4 (0.25–0.69)
C–reactive protein (CRP) mg/dL	1–7 d	M+F	0.27–6.9		d + y: Interval of 0% and 95.0% percentiles. Laboratory investigations were carried out using Roche Hitachi 917, standardized according to CRM 470. Samples of 32–113 children were examined. Lit. /21/
	8 d – < 1 y	M+F	0.10–3.47
	1–3 y	M+F	0.24–5.88
	4–6 y	M+F	0.29–7.53
	7–9 y	M+F	0.24–4.67
	10–12 y	M+F	0.23–5.71
	13–15 y	M+F	0.13–7.40
	16–18 y	M+F	0.19–5.09
Calcium, ionized mg/dL (mmol/L)	Cord blood	M+F	4.72–5.68 (1.18–1.42)		d + y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using ion selective electrode measurement. Lit. /24/
	1 d	M+F	3.92–4.88 (0.98–1.28)
	3 d	M+F	4.12–4.92(1.02–1.24)
	5 d	M+F	4.44–5.28 (1.10–1.38)
	1–20 y	M+F	4.14–5.26 (1.05–1.32)
Calcium, total mg/dL (mmol/L)	0–5 d	M+F	7.9–10.7 (1.96–2.66)		d: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Kodak Ektachem analyzer and ortho-cresolphthalein complexone test. Lit. /23/ y: Interval of 3% and 97% percentiles. Laboratory investigations were carried out using Roche Hitachi 717 and ortho-cresolphthalein complexone test. Samples of (M = 7298; F = 6953) children were examined. Lit. /5/ Taking Abbott Architect as the comparative system and Beckman Coulter, Ortho, Roche and Siemens as the test systems, the value of calcium can not be transferred based on statistical criteria. Lit. /37/
	1.5–2 y	M+F	9.8–11.2 (2.40–2.78)
	3–6 y	M+F	9.5–11.1 (2.36–2.75)
	7–10 y	M+F	9.3–11.0 (2.32–2.74)
	10–14 y	M+F	9.3–10.9 (2.33–2.72)
	14–17 y	M+F	9.2–10.9 (2.30–2.72)
Chloride (mmol/L)	0–7 d	M+F	96–111		d + m + y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Kodak Ektachem Analyzer. Samples of 100 children were examined in every age group. Lit. /22/
	8 d – 1 m	M+F	96–110
	1–6 m	M+F	96–110
	6 m – 1 y	M+F	96–108
	> 1 y	M+F	96–109
Cholesterol mg/dL (mmol/L)	1–2 y	M+F	112–199 (2.89–5.15)		y: Interval of 5% and 95% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Hitachi 917 fully enzymatic cholesterol-oxidase-PAP method. Samples of (M = 5108; F = 4908) children of representative locations all over Germany were selected. Lit. /5/ Consensus: Recommended upper value according to the National Cholesterol Education Program (NCEP) < 200 mg/dl (5.17 mmol/l)
	3–6 y	M+F	123–213 (3.18–5.51)
	7–10 y	M+F	129–213 (3.34–5.51)
	11–13 y	M+F	122–211 (3.15–5.46)
	14–17 y	M+F	117–212 (3.03–5.48)
CK U/L (ukatal/L)	0–90 d	M	29–303 (0.48–5.1)		d, m, y: Interval 2.5% and 97.5% percentiles. Determination at 37 °C according to IFCC. Samples of 60 outpatient and inpatient children were examined in every age group. Lit. /12/
	0–90 d	F	43–474 (0.72–8.3)
	3–12 m	M	25–172 (0.42–2.9)
	3–12 m	F	27–242 (0.45–4.0)
	1–10 y	M+F	25–177 (0.42–3.0)
	11–14 y	M+F	31–172 (0.52–2.9)
	15–18 y	M	28–147 (0.47–2.5)
	15–18 y	F	31–172 (0.52–2.9)
Cortisol (5–11 morning) mg/dL (mmol/L)	0–24 m	M+F	10–34 (28–938)		m, y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Immu-I-analyzer of Bayer Diagnostics. Samples of 32 outpatient and inpatient children were examined in every age group. Lit. /19/
	2–10 y	M+F	10–33 (28–911)
	11–18 y	M+F	10–28 (28–733)
Creatinine mg/dL (umol/L)	1–7 d	M+F	0.20–1.06 (15–80)		d + y: Interval of 2.5% and 97.5% percentiles. A review compared different creatinine tests. 38–69 outpatient and inpatient children were examined in the age groups. Lit. /17/
	8 d – < 1 y	M+F	0.20–0.45 (15–34)
	1–3 y	M+F	0.20–0.41 (15–31)
	4–6 y	M+F	0.28–0.51 (21–39)
	7–9 y	M+F	0.33–0.59 (25–45)
	10–12 y	M+F	0.35–0.75 (27–57)
	13–15 y	M+F	0.40–0.96 (31–73)
	16–18 y	M+F	0.52–0.99 (40–76)
Ferritin (ug/L)	0–1 y	MF	11.5–327		y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Roche Elecsys electrochemiluminescence immunoassay. Samples of 68–139 outpatient and inpatient children were examined. Lit /12/
	> 1–3 y	MF	6.6–61
	4–6 y	MF	6.7–60
	7–12 y	MF	11.2–99
	13–17 y	MF	12.3–89
Folic acid in red cells ug/L (nmol/L)	< 1 y	M	6.3–22.7 (14.3–51.5)		Children ≥ 1.5 y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Diastat HPLC method. Samples of (M =2525; F = 2380) children of representative locations all over Germany were selected. Lit /5/
	< 1 y	F	7.2–22.4 (16.3–50.8)
	2–3 y	M	1.7–15.7 (3.9–35.6)
	2–3 y	F	2.5–15.0 (5.7–34.0)
	4–6 y	M	2.7–14.0 (6.1–31.9)
	4–6 y	F	2.5–13.0 (5.3–29.4)
	7–9 y	M	2.4–13.4 (5.4–30.4)
	7–9 y	F	2.3–11.9 (5.2–27.0)
	10–12 y	M	1.0–10.2 (2.3–23.1)
	10–12 y	F	1.5–10.8 (3.4–24.9)
	13–18 y	M	1.2–7.2 (2.7–16.3)
	13–18 y	F	1.2–8.8 (2.7–19.9)
FT3 ng/L	3.5–6 y	M	3.0–5.1		y: Interval of 3.0% and 97.0% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Elecsys electrochemiluminescence immunoassay. Samples of (M = 6723; F = 6365) children of representative locations all over Germany were selected. Lit. /5/
	3.5–6 y	F	3.2–5.2
	7–10 y	M	3.1–5.1
	7–10 y	F	3.1–5.2
	11–13 y	M	3.1–5.3
	11–13 y	F	3.1–4.9
	14–17 y	M	3.3–4.9
	14–17 y	F	2.8–4.3
FT4 ug/L	5 d	M+F	13–33		d: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Abbott IMX microparticle fluorescence immunoassay. Samples of 141 inpatient children were investigated. Lit. /20/ y: Interval of 3.0% and 97.0% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Elecsys electrochemiluminescence immunoassay. Samples of (M = 6771; F = 6362) children of representative locations all over Germany were selected. Lit. /5/
	3.5–6 y	M	9.8–15.0
	3.5–6 y	F	9.4–15.4
	7–10 y	M	9.6–15.2
	7–10 y	F	9.8–15.0
	11–13 y	M	9.4–14.5
	11–13 y	F	8.9–14.4
	14–17 y	M	8.7–16.3
	14–17 y	F	8.7–15.0
GGT U/L (ukatal/L)	1–7 d	M+F	18–168 (0.30–2.80)		d: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out at 37 °C using Dade Behring Dimension RXL. Samples of > 60 inpatient and outpatient children were investigated. Lit. /11/ y: Interval 2.5% and 97.5% percentiles. Determination at 37 °C according to IFCC. Samples of 58–142 outpatient and inpatient children were examined. Lit. /12/ Taking Abbott Architect as the comparative system and Beckman Coulter, Ortho, Roche and Siemens as the test systems the value of GGT can not be transferred based on statistical criteria Lit. /37/
	0–1 y	M+F	7.8–178 (0.13–2.97)
	> 1–3 y	M+F	2.4–21.0 (0.04–0.35)
	4–6 y	M+F	3.0–21.0 (0.05–0.35)
	7–12 y	M+F	6.0–24.0 (0.10–0.40)
	13–17 y	M	9.0–42.6 (0.15–0.71)
	13–17 y	F	3.6–25.8 (0.06–0.43)
GLD U/L (ukatal/L)	1–30 d	M+F	< 10 (0.17)		d, m, y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out at 25 °C according to the German Association of Clinical Chemistry. Samples of 25 outpatient and inpatient children were examined in every age group. Lit. /14/. A conversion of 25 °C to 37 °C was achieved according to Lit. /13/.
	1–6 m	M+F	< 7 (0.12)
	7–12 m	M+F	< 6 (0.10)
	2–3 y	M+F	< 4 (0.07)
	4–16 y	M+F	< 5 (0.08)
HbA_1C % (mmol HbA_1C/ mmol Hb)	1.5–2 y	M	3.9–5.6 (19–38)	4.8 (29)	From 1.5 y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Diastat HPLC method. Samples of (M =7217: F = 6881) children of representative locations all over Germany were selected. Lit. /5/
	1.5–2 y	F	3.7–5.6 (17–38)	4.7 (28)
	3–6 y	M	4.0–5.6 (20–38)	4.9 (30)
	3–6 y	F	4.0–5.5 (20–37)	4.6 (27)
	7–10 y	M	4.1–5.7 ( 21–39)	4.6 (27)
	7–10 y	F	4.1–5.6 (21–38)	4.6 (27)
	11–13 y	M	4.1–5.7 (21–39)	4.6 (27)
	11–13 y	F	4.1–5.6 (21–38)	4.6 (27)
	14–17 y	M	4.1–5.6 (21–38)	4.9 (30)
	14–17 y	F	4.1–5.6 (21–38)	4.8 (29)
HDL-Cholesterol mg/dL (mmol/L)	1–2 y	M+F	28.1–68.6 (0.73–1.77)		y: Interval of 5% and 95% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Hitachi 917 fully enzymatic cholestrol-oxidase-PAP method. Samples of (M =7297; F = 6952) children of representative locations all over Germany were selected. Lit. /5/ Consensus: Low HDL-cholesterol according to the National Cholesterol Education Program (NCEP) < 35 mg/dl (0.91 mmol/l).
	3–6 y	M+F	35.2–77.4 (0.91–2.00)
	7–10 y	M+F	39.6–81.7 (1.02–2.11)
	11–13 y	M+F	38.3–80.9 (0.90–2.09)
	14–17 y	M+F	36.5–77.4 (0.94–2.00)
Homocysteine (umol/L)	1.5–2 y	M	3.8–9.9	6.1	From 1.5 y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Abbott IMX fluorescence particle immunoassay. Samples of (M = 7159; F = 6809) children of representative locations all over Germany were selected. Lit. /5/
	1.5–2 y	F	3.6–8.7	5.8
	3–6 y	M	3.7–8.8	5.7
	3–6 y	F	3.6–8.3	5.6
	7–10 y	M	4.1–9.8	6.3
	7–10 y	F	3.9–9.5	6.1
	11–13 y	M	4.6–12.1	7.2
	11–13 y	F	4.3–11.0	6.3
	14–17 y	M	5.2–19.8	8.8
	14–17 y	F	4.6–13.4	7.8
Iron ug/dL (umol/L)	Up to 2 y	M	12–133 (2.1–23.8)		y: Interval of 5% and 95% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Hitachi 917 ferrozin method. Samples of (M = 7292; F = 6948) children of representative locations all over Germany were selected. Lit. /5/
	Up to 2 y	F	19–140 (3.4–25.1)
	3–6 y	M	17–142 (3.0–25.4)
	3–6 y	F	21–139 (3.8–24.9)
	7–10 y	M	26–138 (4.7–24.7)
	7–10 y	F	28–137 (5.0–24.5)
	11–13 y	M	32–150 (5.5–26.9)
	11–13 y	F	33–148 (5.8–26.4)
	14–17 y	M	36–195 (6.4–35.0)
	14–17 y	F	29–173 (5.2–30.9)
Lactate dehydrogenase U/L (ukatal/L)	0–1 y	M+F	196–438 (3.27–7.3)		y: Interval of 2.5% and 97.5% percentiles o f the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out at 37 °C according to IFCC. Samples of 75–204 inpatient and outpatient children were investigated. Lit. /12/
	> 1–3 y	M+F	105–338 (1.75–5.6)
	4–6 y	M+F	107–314 (1.78–5.2)
	7–12 y	M+F	112–307 (1.87–5.1)
	13–17 y	M+F	115–287 (1.94–4.78)
LDL-Cholesterol mg/dL (mmol/L)	1–2 y	M+F	55–134 (1.422–3.46)		y: Interval of 5% and 95% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Hitachi 917 fully enzymatic cholesterol oxidase-PAP method. Samples of (M = 7291; F = 6942) children of representative locations all over Germany were selected. Lit. /5/ Consensus: Normal LDL-cholesterol according to the National Cholesterol Education Program (NCEP) < 130 mg/dl (3.36 mmol/l).
	3–6 y	M+F	60–141 (1.552–3.65)
	7–10 y	M+F	60–138 (1.552–3.57)
	11–13 y	M+F	55–136 (1.422–3.52)
	14–17 y	M+F	54–135 (1.396–3.49)
Lipase U/L (ukatal/L)	< 1 y	M+F	0–29 (0–0.49)		y: Interval of 2.5% and 97.5% percentiles. The method at 37 °C using Hitachi 917 analyzer is based on the splitting of methylresorufinester. Samples of 40–121 inpatient and outpatient children were invetigated in the age groups. Lit. /15/
	1–12 y	M+F	10–37 (0.17–0.61)
	13–18 y	M+F	11–46 (0.19–0.76)
Magnesium mg/dL (mmol/L)	Newborn	M+F	1.1–2.6 (0.45–1.07)		y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Hitachi 917 xylidylblue method. Samples of (M = 7279; F = 6932) children of representative locations all over Germany were selected. Lit. /5/ Taking Abbott Architect as the comparative system and Beckman Coulter, Ortho, Roche and Siemens as the test systems the value of magnesium can not be transferred based on statistical criteria Lit. /37/
	1.5–2 y	M	1.1–2.1 (0.45–0.82)
	1.5–2 y	F	1.1–2.1 (0.45–0.82)
	3–17 y	M+F	1.1–2.1 (0.45–0.82)
Pankreatic Amylase (U/L)	< 1 y	M+F	0–8 (0–0.13)		y: Interval of 2.5% and 97.5% percentiles. The method at 37 °C using Roche Hitachi 917 analyzer is based on G7 amylase method according to IFCC. Samples of 40–121 inpatient and outpatient children were investigated. Lit. /15/
	1–12 y	M+F	5–31 (0.09–0.52)
	10–18 y	M+F	7–39 (0.11–0.65)
Phosphor mg/dL (mmol/L)	1–30 d	M+F	3.9–7.7 (1.25–2.50)		d, m: Ammonium phosphomolybdat method. Lit. /34/ y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Hitachi 917 ammonium phosphomolybdat method. Samples of (M = 7294; F = 6944) children of representative locations all over Germany were selected. Lit. /5/ Taking Abbott Architect as the comparative system and Beckman Coulter, Ortho, Roche and Siemens as the test systems the value of phosphor can not be transferred based on statistical criteria Lit. /37/
	1–12 m	M+F	3.5–6.6 (1.15–2.15)
	1.5–2 y	M	4.7–6.6 (1.51–2.15)
	1.5–2 y	F	4.6–6.6 (1.49–2.15)
	3–6 y	M	4.4–6.2 (1.41–1.99)
	3–6 y	F	4.4–6.2 (1.42–1.99)
	7–10 y	M	4.3–5.9 (1.39–1.91)
	7–10 y	F	4.2–6.0 (1.37–1.93)
	11–13 y	M	4.1–5.8 (1.32–1.87)
	11–13 y	F	4.1–6.2 (1.32–1.99)
	14–17 y	M	3.9–5.3 (1.27–1.71)
	14–17 y	F	3.6–5.0 (1.16–1.61)
Potassium (mmol/L)	0–7 d	M+F	3.2–5.5		d, m, y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Kodak Ektachem Analyzer. Samples of 100 inpatient children were investigated. Lit. /22/
	8 d – 1 m	M+F	3.4–6.0
	1–6 m	M+F	3.5–5.6
	6 m– 1 y	M+F	3.5–5.1
	> 1 y	M+F	3.3–4.6
Protein (total) (g/L)	1.5–2 y	M+F	61–76		y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Roche Hitachi 917 Biuret reaction without deproteinization of serum. Samples of (M = 7254; F = 6905) children of representative locations all over Germany were selected. Lit. /5/
	3–6 y	M+F	63–81
	7–10 y	M+F	66–82
	11–13 y	M+F	68–83
	14–17 y	M+F	68–85
Selen umol/L	< 30 d	M+F	0.19–1.35		d, m, y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using elektrothermal atomic absorption spektrophotometry (ET-AAS). Samples of (M = 532; F = 478) children were investigated. Lit. /35/
	1–2 m	M+F	0.19–1.27
	2–4 m	M+F	0.13–1.18
	4–12 m	M+F	0.17–1.47
	1–5 y	M+F	0.43–1.63
	5–18 y	M+F	0.53–1.57
Sodium (mmol/L)	0–7 d	M+F	133–146		d, m, y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Kodak Ektachem Analyzer. Samples of 100 children were investigated in every age group. Lit. /22/
	8 d – 1 m	M+F	134–144
	1–6 m	M+F	134–142
	6 m – 1 y	M+F	133–142
	> 1 y	M+F	134–143
Soluble transferrin receptor (sTFR) mg/L	0–1 y	M+F	1.55–5.7		y: Interval of 2.5% and 97.5% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Elecsys electrochemiluminescence immunoassay. Samples of 46–189 inpatient and outpatient children were investigated. Lit. /12/
	> 1–3 y	M+F	1.65–5.6
	4–6 y	M+F	1.47–5.4
	7–12 y	M+F	1.95–5.5
	13–17 y	M+F	1.76–5.9
Trace elements (expected values in serum)		M+F	Cobalt (Co)	< 1 ug/L	Expected values for adults and children: Lit. /18/
		M+F	Chromium (Cr)	< 1 ug/L
		M+F	Copper (Cu)	1 mg/L
		M+F	Iron	1 mg/L
		M+F	Manganese (Mn)	< 1 ug/L
		M+F	Molybdenum (Mo)	< 1 ug/L
		M+F	Nickel (Ni)	< 1 ug/L
		M+F	Selenium (Se)	80 ug/L
		M+F	Silicon (Si)	< 10 ug/L
		M+F	Tin (Sn)	< 1 ug/L
		M+F	Vanadium (V)	< 1 ug/L
		M+F	Zink (Zn)	1 mg/l
Triglycerides mg/dL (mmol/L)	1–2 y	M+F	45–247 (0.51–2.82)		y: Interval of 5% and 95% perzentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Hitachi 717 GPO-PAP method. Samples of (M 89-100; F 92-101) children of representative locations all over Germany were selected. Lit. /16/ Consensus: Normal triglycerides according to the National Cholesterol Education Program (NCEP) < 150 mg/dl (1.71 mmol/l).
	3–6 y	M+F	42–220 (0.47–2.52)
	7–10 y	M+F	42–217 (0.47–2.48)
	11–13 y	M+F	42–227 (0.47–2.59)
	14–17 y	M+F	44–235 (0.50–2.67)
TSH mU/L	5 d	M+F	0.5–7.9		d: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Abbott IMX micro particle fluorescence Immunoassay. Samples of 141 inpatient children were investigated. Lit. /20/ y: Interval of 3.0% and 97.0% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Elecsys electrochemiluminescence immunoassay. Samples of (M = 6723; F = 6366) children of representative locations all over Germany were selected. Lit. /5/
	3.5–6 y	M	1.0–5.5
	3.5–6 y	F	1.0–5.2
	7–10 y	M	1.0–5.2
	7–10 y	F	1.0–5.2
	11–13 y	M	0.9–4.8
	11–13 y	F	0.9–4.5
	14–17 y	M	0.8–4.0
	14–17 y	F	0.7–4.0
Uric acid mg/dL (umol/L)	1–30 d	M	1.0–4.6 (59–271)		Up to 1 y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out at 37 °C using Dade Behring Dimension RXL uricase-PAP method. Samples of > 100 inpatient and outpatient children were investigated in every age group. Lit. /19/ (Abstract)
	1–30 d	F	1.2–3.9 (71–232)
	31 d–1 y	M	1.1–5.4 (65–319)
	31 d–1 y	F	1.2–5.6 (71–330)
	1.5–3 y	M+F	2.2–5.2 (131–309)	3.6 (214)	From 1.5 y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Hitachi 917 uricase PAP reaction. Samples of (M =7298; F = 6951) children of representative locations all over Germany were selected. Lit. /5/
	3–6 J	M+F	2.3–5.3 (137–315)	3.6 (214)
	7–10 y	M	2.3–5.6 (137–333)	3.7 (220)
	7–10 y	F	2.4–5.7 (143–339)	3.8 (226)
	11–14 y	M	2.5–7.7 (149–458)	4.6 (274)
	11–14 y	F	2.6–6.2 (155–369)	4.3 (256)
	15–17 y	M	3.7–8.0 (220–476)	5.1 (303)
	15–17 y	F	2.8–6.0 (167–357)	4.2 (250)
Vitamin B12 ng/L (pmol/L)	0–1 y	M	293–1210 (216–891)		Up to 1 y: Interval of 2.5% and 97.5% percentiles. Lit. /36/ From 3.5 y: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Roche Elecsys electrochemiluminescence immunoassay. Samples of (M = 6349; F = 6701) children of representative locations all over Germany were selected. Lit. /5/
	0–1 y	F	228–1515 (168–1118)
	3.5–6 y	M	457–1825 (338–1347)	991 (738)
	3.5–6 y	F	484–1882 (357–1340)	1009 (745)
	7–10 y	M	427–1610 (315–1188)	890 (675)
	7–10 y	F	427–1562 (319–1153)	874 (645)
	11–13 y	M	366–1322 (270–976)	740 (546)
	11–13 y	F	360–1397 (262–1031)	738 (545)
	14–17 y	M	291–1154 (215–852)	587 (433)
	14–17 y	F	291–1167 (215–861)	602 (444)
Calcitonin (pg/mL)	0–1 y	M + F	155		Immunometric assay using Immulite XPi 2000; Siemens. Presented are the mean serum concentrations published in Reference /48/. Elevated serum calcitonin is an indicator of hereditary medullary thyroid carcinoma (MTC) caused by germline mutations of the RET protooncogene /49/.
	1–2 y	M + F	126
	2–3 y	M + F	M 119/F 74
	3–4 y	M + F	89
	4–5 y	M + F5	M 130/F 95
	5–6 y	M + F	M 114/F 93
	6–7 y	M + F	M 86/F 105
	7–8 y	M + F	M 97/F 90
	8–9 y	M + F	M 61/F 80
	9–10 y	M + F	M 65/F 73

Table 54-2 Reference intervals and orienting ranges of “normal” for hematological analytes

Parameter	Age (d, days; w, weeks; m, months; y, years)	Sex (M, male; F, female)	Median	Reference interval	Comment
Eosinophil count (10⁹/L)	Fetuses				Up to week 27: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus II. Samples of 17 fetuses were investigated. Lit. /30/
	16–19 w	M+F	0.02	< 0.06
	20–27 w	M+F	0.08	< 0.10
	Newborn	M+F	0.4	< 1.00
	Children				From the age of 4 years: Interval of 3% and 97% percentiles. Laboratory investigations were carried out using Coulter STKR. Samples of 25–108 children were investigated. Lit. /31/
	4–6 y	M+F	0.24	0.06–0.90
	7–8 y	M+F	0.27	0.08–1.0
	9–12 y	M+F	0.21	0.06–1.12
	13–14 y	M+F	0.18	0.05–0.61
	15–19 y	M+F	0.17	0.05–0.57
Erythrocyte count (10¹²/L)	Fetuses				Up to week 17: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Coulter S plus. Samples of 116 fetuses were investigated .Lit. /26/
	15 w	M+F		2.2–3.2
	16 w	M+F		2.3–3.2
	17 w	M+F		2.6–3.6
	18–21 w	M+F		2.4–3.8	Up to 30 weeks: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S plus II .Samples of 2860 fetuses were investigated. Lit. /27/
	22–25 w	M+F		2.7–4.3
	26–29 w	M+F		2.5–5.1
	> 30 w	M+F		4.3–6.3
	Children				Up to 12 months: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S plus II. Capillary blood of 440 children was investigated. Lit. /28/
	1 d	M+F		3.9–5.9
	0.3 m	M+F		3.3–5.3
	1 m	M+F		3.1–4.3
	2 m	M+F		3.5–5.1
	4 m	M+F		3.9–5.5
	6 m	M+F		4.0–5.3
	9–12 m	M+F	4.5	3.7–5.3
	1.5–2 y	M+F	4.6	4.0–5.1	From the age of 1.5 years: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigation was carried out using Abbott Cell-Dyn 3500. Samples of (M = 7204; F = 6869) children of representative locations all over Germany were investigated. Lit. /5/.
	3–6 y	M	4.6	4.0–5.1
	3–6 y	F	4.7	4.0–5.1
	7–10 y	M	4.6	4.0–5.2
	7–10 y	F	4.7	4.0–5.1
	11–13 y	M	4.6	4.1–5.3
	11–13 y	F	5.0	4.1–5.3
	14–17 y	M	4.5	4.2–5.7
	14–17 y	F	4.5	4.0–5.0
Hematocrit (Fraction)	Fetuses				Up to 1.5 years: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S plus II. Capillary blood of 116 fetuses was investigated. Lit. /25, 26/. In a study /38/ the effect of prenatal age on hematocrit is described between 22 and 40 weeks. For every week advance in gestational age (GA) the hematocrit increased according to the formula hematocrit = 0.2859 + (GA × 0.006359).
	15 w	M+F		0.28–0.42
	16 w	M+F		0.34–0.42
	17 w	M+F		0.31–0.43
	18–21 w	M+F		0.31–0.45
	22–25 w	M+F		0.31–0.47
	26–29 w	M+F		0.32–0.50
	> 30 w	M+F		0.30–0.58
	Cord blood	M+F		0.48–0.56
	Children
	1 d	M+F		0.44–0.68
	2–6 d	M+F		0.40–0.70
	1–2 w	M+F		0.38–0.70
	2–3 w	M+F		0.38–0.60
	3–7 w	M+F		0.36–0.46
	7–12 w	M+F		0.30–0.38
	10–12 m	M+F	35	0.35–0.43
	1.5–3 y	M	35	0.31–0.39	From the age of 1.5 years: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigation was carried out using Abbott Cell-Dyn 3500. Samples of (M = 7206; F = 6870) children of representative locations all over Germany were investigated. Lit. /5/.
	1.5–3 y	F	35	0.31–0.39
	4–6 y	M	35	0.32–0.42
	4–6 y	F	36	0.32–0.40
	7–10 y	M	36	0.33–0.42
	7–10 y	F	36	0.33–0.42
	11–13 y	M	40	0.34–0.44
	11–13 y	F	38	0.34–0.43
	14–17 y	M	42	0.36–0.48
	14–17 y	F	39	0.35–0.44
Hemoglobin concentration g/dL (mmol/L)	Fetuses				Up to week 17: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S plus cyanomethemoglobin method. Capillary blood of 116 fetuses was investigated. Lit. /26/
	15 w	M+F	10.9 (6.77)	9.5–12.3 (5.90–7.64)
	16 w	M+F	12.5 (7.76)	10.9–14.1 (6.77–8.76)
	17 w	M+F	12.4 (7.70)	10.6–14.0 (6.58–8.69)
	18–21 w	M+F	11.7 (7.27)	9.5–14.1 (5.90–8.76)	Up to week 30: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S plus cyanomethemoglobin method. Samples of capillary blood of 2860 fetuses was investigated. Lit. /27/ In a study /38/ the effect of prenatal age on hemoglobin is described between 22 and 40 weeks. For every week advance in gestational age (GA) the hemoglobin concentration in the blood increased according to the formula hemoglobin = 9.92 + (GA × 0.2087)
	22–25 w	M+F	12.2 (7.57)	9.4–14.7 (5.84–9.13)
	26–29 w	M+F	12.9 (8.01)	10.1–15.7 (6.27–9.75)
	> 30 w	M+F	13.6 (8.45)	9.2–18.0 (5.71–11.18)
	Cord blood	M+F		13.5–20.7 (8.38–12.86)
	Children				Up to 13.5 months: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S plus cyanomethemoglobin method. Samples of capillary blood of 760 children were investigated. Lit. /29/
	2–6 d	M+F		15.0–24.0 (9.32–14.90)
	14–23 d	M+F		12.7–18.1 (7.89–11.24)
	24–37 d	M+F		10.3–17.9 (6.40–11.12)
	40–50 d	M+F		9.0–16.6 (5.59–10.31)
	2.0–2.5 m	M+F		9.2–15.0 (5.71–9.32)
	3.0–3.5 m	M+F		9.6–12.8 (5.96–7.95)
	5–7 m	M+F		10.1–12.9 (6.27–8.01)
	8–10 m	M+F		10.5–12.9 (6.52–8.01)
	11–13.5 m	M+F		10.7–11.3 (6.64–7.02)
	1.5–3 y	M+F		10.8–12.8 (6.71–7.95)	From the age of 1.5 years: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigations were carried out using Abbott Cell-Dyn 3500 cyanomethemoglobin method. Samples of (M = 7205 and F = 6870) children of representative locations all over Germany were investigated. Lit. /5/.
	3–6 y	M	12.3 (7.64)	10.5–13.8 (6.52–8.57)
	3–6 y	F	12.3 (7.64)	10.6–13.7 (6.58–8.51)
	7–10 y	M	12.8 (7.95)	11.2–14.3 (6.96–8.88)
	7–10 y	F	12.7 (7.89)	11.2–14.2 (6.96–8.82)
	11–13 y	M	13.2 (8.20)	11.6–15.0 (7.20–9.32)
	11–13 y	F	12.6 (7.82)	11.6–14.5 (7.20–9.00)
	14–17 y	M	14.5 (9.00)	12.1–17.0 (7.51–10.56)
	14–17 y	F	13.7 (8.51)	11.6–14.8 (7.20–9.19)
Leukocyte count (10³/uL)	Fetuses				Fetuses and newborn: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of of 17 fetuses were investigated. Lit. /29/
	16–19 w	M+F		3.1–6.3
	20–27 w	M+F		2.5–6.2
	Newborn	M+F		8.1–20.1
	Children				From the age of 4: Interval of 3% and 97% percentiles Laboratory investigation was carried out using Coulter STKR. Samples of 25–108 children were investigated. Lit. /30/
	4–6 y	M	7.5	4.8–11.5
	4–6 y	F	7.0	5.0–12.1
	7–8 y	M	7.0	4.5–10.5
	7–8 y	F	7.4	5.2–11.7
	9–10 y	M	6.2	4.4–10.6
	9–10 y	F	6.9	4.7–10.0
	11–12 y	M	6.1	4.0–9.6
	11–12 y	F	6.7	4.8–10.4
	13–14 y	M	6.0	4.2–9.3
	13–14 y	F	6.6	4.5–10.7
	17–18 y	M	6.1	4.2–12.2
	15–19 y	F	6.9	4.2–10.6
Lymphocyte count (10³/uL)	Fetuses				Fetuses and newborn: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of of 17 fetuses were investigated. Lit. /29/
	16–19 w	M+F	1.9	0.5–3.3
	20–27 w	M+F	2.6	1.2–4.0
	Newborn	M+F	5.6	3.6–7.6
	Children				From the age of 4: Interval of 3% and 97% percentiles Laboratory investigation was carried out using Coulter STKR. Samples of 25–108 children were investigated. Lit. /30/
	4–6 y	M+F	2.2	1.7–4.2
	7–8 y	M+F	2.6	1.7–4.1
	9–10 y	M	2.4	1.6–4.0
	9–10 y	F	2.4	1.7–3.9
	11–12 y	M+F	2.3	1.5–3.7
	13–14 y	M+F	2.4	1.4–3.6
	15–16 y	M+F	2.2	1.3–3.4
	17–19 y	M+F	2.2	1.3–3.0
Mean cellular hemoglobin concentration of erythrocytes (g/L)	Blood cord	M+F		310–350
	Children				Up to year 3: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 2860 children were investigated. Lit. /23/
	1 d	M+F		310–350
	0.3 m	M+F		260–340
	1 m	M+F		250–340
	2 m	M+F		260–340
	3–3.5 m	M+F		260–340
	5–7 m	M+F		260–340
	8–10 m	M+F		280–320
	11–13.5 m	M+F		280–320
	1.5–3 y	M+F		260–340
	3–6 y	M	341	322–355	From the age of 3 years: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigation was carried out using Abbott Cell-Dyn 3500 method. Samples of (M = 7206 ; F = 6870) children of representative locations all over Germany were investigated. Lit. /5/.
	3–6 y	F	339	323–355
	7–10 y	M	347	325–356
	7–10 y	F	349	325–355
	11–13 y	M	341	326–356
	11–13 y	F	345	325–354
	14–17 y	M	342	327–357
	14–17 y	F	339	325–353
Mean corpuscular erythrocyte volume (femtoliter)	Fetuses				Up to week 17: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 15–21 fetuses were investigated. Lit. /21/
	15 w	M+F		127–159
	16 w	M+F		119–167
	17 w	M+F		121–153
	18–21 w	M+F		119–143	Up to week 30: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 2860 fetuses were investigated. Lit. /26/
	22–25 w	M+F		109–141
	26–29 w	M+F		103–134
	> 30 w	M+F		97–132
	Children				Up to 13.5 months: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 2860 fetuses were investigated. Lit. /27/
	1 T	M+F		98–122
	0.3 m	M+F		84–128
	1 m	M+F		82–126
	2 m	M+F		81–121
	3–3.5 m	M+F		77–113
	5–7 m	M+F		73–109
	8–10 m	M+F		74–106
	11–13.5 m	M+F		74–102
	1.5–2 y	M+F		73–101	From year 1.5: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigation was carried out using Abbott Cell-Dyn 3500 method. Samples of (M = 7204 ; F = 6869) children of representative locations all over Germany were investigated. Lit. /5/.
	3–6 y	M	80	71–86
	3–6 y	F	81	72–86
	7–10 y	M	82	75–88
	7–10 y	F	83	75–89
	11–13 y	M	83	77–89
	11–13 y	F	84	77–90
	14–17 y	M	85	78–93
	14–17 y	F	86	78–93
Mean cellular hemoglobin content (picogram)	Fetuses				Up to year 3: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 2860 children were investigated. Lit. /27/
	15 w	M+F		127–159
	16 w	M+F		119–167
	17 w	M+F		121–153
	18–21 w	M+F		119–143
	22–25 w	M+F		109–141
	26–29 w	M+F		103–134
	> 30 w	M+F		97–132
	Children
	Blood cord	M+F		101–125
	1 d	M+F		98–122
	0.3 m	M+F		84–128
	1 m	M+F		82–126
	2 m	M+F		81–121
	3–3.5 m	M+F		77–113
	5–7 m	M+F		73–109
	8–10 m	M+F		74–106
	11–13.5 m	M+F		74–102
	1.5–3 y	M+F		73–101
	3–6 y	M	80	71–86	From the age of 4 years: Interval of 3% and 97% percentiles of the German survey on children‘s health (KIGGS study) are shown. Laboratory investigation was carried out using Abbott Cell-Dyn 3500 method. Samples of (M = 7206 ; F = 6870) children of representative locations all over Germany were investigated. Lit. /5/.
	3–6 y	F	81	72–86
	7–10 y	M	82	75–88
	7–10 y	F	83	75–89
	11–13 y	M	83	77–89
	11–13 y	F	84	77–90
	14–17 y	M	85	78–93
	14–17 y	F	86	78–93
Monocyte count (10³/uL)	Fetuses				Fetuses and newborn: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 17 children of every age group were investigated. Lit. /29/
	16–19 w	M+F	0.1	< 0.30
	20–27 w	M+F	0.2	< 0.40
	Newborn	M+F	0.9	0.1–1.7
	Children				From the age of 4 years: Interval of 3% and 97% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 25–108 children were investigated. Lit. /30/
	4–6 y	M+F	0.62	0.33–1.16
	7–8 y	M+F	0.60	0.33–1.21
	9–10 y	M+F	0.58	0.33–1.00
	11–12 y	M	0.55	0.31–0.92
	11–12 y	F	0.61	0.36–1.00
	13–14 y	M	0.53	0.26–0.87
	13–14 y	F	0.59	0.38–1.00
	15–19 y	M	0.55	0.33–0.86
	15–19 y	F	0.65	0.35–1.06
Neutrophil leukocyte count (10³/uL)	Fetuses				Fetuses and newborn: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 17 children of every age group were investigated. Lit. /29/
	16–19 w	M+F	0.2	0.1–0.3
	20–27 w	M+F	0.2	0.1–0.3
	Newborn	M+F	6.5	3.1–9.9
	Children				From the age of 4 years: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 25–108 children were investigated Lit. /30/
	4–6 y	M+F	3.2	1.8–7.6
	7–8 y	M+F	3.4	1.8–7.4
	9–10 y	M	2.7	1.7–6.1
	9–10 y	F	3.2	1.7–6.4
	11–12 y	M	2.7	1.6–5.6
	11–12 y	F	2.7	1.6–5.6
	13–14 y	M	2.6	1.7–5.4
	13–14 y	F	3.3	1.8–7.2
	15–18 y	M	2.9	1.8–6.1
	15–18 y	F	3.4	1.8–6.5
Reticulocyte count (10³/uL)			Absolute	Relative (%)	* Absolute and relative values. Laboratory investigation was carried out using FACS Calibur. Samples of 14–63 children in every age group were determined. Lit. /28/. ** Absolute and relative values. Laboratory investigation was carried out using Sysmex R-1000. Samples of 30–750 children in every age group were determined. Lit. /28/.
	0–14 d	M+F	239–404*	1.6–8.3
	14 d – 1 y	M+F	46–138*	1.1–3.0
	1–3 y	M+F	50–141*	1.1–5.0
	3–8 y	M+F	45–163*	0.95–.03
	8–12 y	M+F	55–154*	1.18–3.78
	> 12 y	M+F	59–146*	1.32–4.91
	Newborn	M+F	49–150**	1.1–5.5
	Premature babies	M+F	40–171**	0.9–6.5
	1–16 y	M+F	50–65**	0.6–1.9
Thrombocyte count (10³/uL)	Fetuses				Fetuses and newborn: Interval of 2.5% and 97.5% percentiles.Laboratory investigation was carried out using Coulter S Plus. Samples of 17 children in every age group were investigated. Lit. /29/ According to a study /39/ platelet counts increased with advancing gestational age (GA). At GA of 22 weeks the thrombocyte count of 200 × 10⁹/l increased in mean platelet count by 2089/ul every week..
	16–19 w	M+F		123–237
	20–27 w	M+F		176–260
	Newborn	M+F		214–381
	Children				From the age of 4 years: Interval of 3% and 97% percentiles. Laboratory investigation was carried out using Coulter S Plus. Samples of 40–107 children were investigated in every age group. Lit. /30/
	4 + 5 y	M	259	256–351
	4 + 5 y	F	268	265–382
	6 y	M	250	248–349
	6 y	F	253	253–257
	7 y	M	246	180–349
	7 y	F	234	159–361
	8 y	M	240	171–343
	8 y	F	239	195–321
	9 y	M	246	162–310
	9 y	F	247	178–307
	10 y	M	230	148–355
	10 y	F	242	180–314
	11 y	M	234	159–342
	11 y	F	243	162–317
	12 y	M	233	159–342
	12 y	F	238	162–317
	13 y	M	237	159–342
	13 y	F	251	171–355
	14 y	M	231	160–332
	14 y	F	263	171–355
	17+18 y	M	263	175–331
	18–19 y	F	241	159–318

Table 54-3 Reference intervals and orienting ranges of “normal“ for hemostaseological analytes

Parameter	Age (d. days; w. weeks; m. months; y. years)	Sex	Reference interval	Median	Comment
Activated partial thromboplastin time (APTT) (sec.)	Fetuses				Fetuses and newborn: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 22 fetuses/newborn were investigated in the age groups. Lit. /31/
	19–23 w	M+F	83–250	168.8
	24–29 w	M+F	87–210	154.0
	30–38 w	M+F	76–128	104.8
	Newborn	M+F	35–52	44.3	Children d: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 44-77 children were investigated in the age groups. Lit. /32. 33/ Children m, y: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT coagulation test. Samples of 40–242 children were investigated in the age groups. Lit. /40/
	Children
	1 d	M+F	31.3–54.5	42.9
	5 d	M+F	25.4–59.8	42.6
	1–3 m	M+F	26.5–52.5	39
	4–6 m	M+F	31.0–46.0	36
	7–12 m	M+F	25.0–42.0	35
	13 m – 4 y	M+F	28.0–43.0	33
	5–9 y	M+F	27.0–42.0	34
	10–18 y	M+F	28.0–45.0	34
Antithrombin (U/mL)	Children				1 m to 18 y: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT coagulation test. Samples of 40-242 children were investigated in the age groups. Lit. /40/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1–3 m	M+F	048–1.28	0.93
	4–6 m	M+F	0.76–1.26	1.04
	7–12 m	M+F	0.92–1.34	1.12
	13 m – 4 y	M+F	0.93–1.33	1.12
	5–9 y	M+F	0.88–1.31	1.10
	10–18 y	M+F	0.87–1.27	1.10
Factor V (U/mL)	Children				Children and adults: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 44–77 children were investigated in the age groups. Lit. /32. 33/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1 d	M+F	0.41–1.44	0.88
	5 d	M+F	0.46–1.54	1.00
	1 m	M+F	0.48–1.56	1.02
	3 m	M+F	0.59–1.39	0.99
	6 m	M+F	0.58–1.46	1.02
	Adults	M+F	0.62–1.50	1.06
Factor VII (U/mL)	Children				Children and adults: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 44–77 children were investigated in the age groups. Lit. /32, 33/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1 d	M+F	0.21–1.13	0.67
	5 d	M+F	0.30–1.38	0.84
	1 m	M+F	0.21–1.45	0.83
	3 m	M+F	0.31–1.43	0.87
	6 m	M+F	0.47–1.51	0.99
	Adults	M+F	0.67–1.43	1.05
Factor VIII:C (U/mL)	Children				Children 1 m to 18 y: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT one-step factor testing with the use of FVIII-deficient plasma. Samples of 40–242 children were investigated in the age groups. Lit. /40/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1–3 m	M+F	0.65–2.01	0.96
	4–6 m	M+F	0.70–1.53	0.93
	7–12 m	M+F	0.60–1.80	1.17
	13 m – 4 y	M+F	0.70–1.95	1.13
	5–9 y	M+F	0.74–1.90	1.10
	10–18 y	M+F	0.68–2.02	1.19
Factor IX (U/mL)	Newborn				Newborn, children and adults: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 44–77 children were investigated in the age groups. Lit. /32, 33/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1 d	M+F	0.11–0.71	0.41
	5 d	M+F	0.19–0.83	0.51
	1 m	M+F	0.20–0.92	0.56
	3 m	M+F	0.35–0.99	0.67
	6 m	M+F	0.35–1.19	0.77
	Adults	M+F	0.70–1.52	1.06
Factor X (U/mL)	Newborn				Newborn, children and adults: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 44–77 children were investigated in the age groups. Lit. /32, 33/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1 d	M+F	0.35–1.27	0.81
	5 d	M+F	0.68–1.58	1.10
	1 m	M+F	0.57–1.57	1.07
	3 m	M+F	0.75–1.67	1.21
	6 m	M+F	0.67–1.63	1.15
	Adults	M+F	0.57–1.37	0.97
Fibrinogen (g/L)	Fetuses				Fetuses: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Diagnostica Stago coagulation test according to Clauss. Samples of 22 children were investigated in the age groups. Lit. /31/
	19–23 w	M+F	0.57–1.50	0.85
	24–29 w	M+F	0.65–1.65	1.12
	30–38 w	M+F	1.25–1.65	1.35
	Children				Children: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT Multifibrin reagent according to Clauss. Samples of 40–242 children were investigated in the age groups. Lit. /40/
	1–3 m	M+F	1.50–3.62	2.38
	4–6 m	M+F	1.75–4.16	2.37
	7–12 m	M+F	1.98–5.29	2.45
	13 m – 4 y	M+F	2.14–3.96	2.55
	5–9 y	M+F	2.08–3.98	2.62
	10–18 y	M+F	2.12–4.37	2.63
International Normalized Ratio (INR)	1–3 m	M+F	0.90–1.17	1.06	Children: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT Thromborel S. Samples of 40–242 children were investigated in the age groups. Lit. /40/
	4–6 m	M+F	0.96–1.17	1.04
	7–12 m	M+F	0.95–1.13	1.04
	13 m – 4 y	M+F	0.94–1.13	1.05
	5–9 y	M+F	0.98–1.14	1.08
	10–18 y	M+F	0.98–1.20	1.10
Protein C (U/mL)	1–3 m	M+F	0.27–0.80	0.51	Children: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCT/BCS Berichrom Protein. Samples of 40–242 children were investigated in the age groups. Lit. /40/. The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	4–6 m	M+F	0.40–0.92	0.65
	7–12 m	M+F	0.47–1.13	0.75
	13 m – 4 y	M+F	0.67–1.30	0.89
	5–9 y	M+F	0.66–1.28	0.93
	10–18 y	M+F	0.60–1.42	0.92
Prothrombin time (sec.)	Fetuses				Fetuses: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Diagnostica Stago coagulation test. Samples of 22 children were investigated in the age groups. Lit. /31/
	19–23 w	M+F	19–45	32.5
	24–29 w	M+F	19–44	32.2
	30–38 w	M+F	16–30	22.6
	Children	M+F	12–24	16.7	Children: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT Thromborel S. Samples of 40–242 children were investigated in the age groups. Lit. /40.
	1–3 m	M+F	10.6–14.9	13.1
	4–6 m	M+F	11.3–14.9	13.0
	7–12 m	M+F	11.4–14.0	13.1
	13 m – 4 y	M+F	11.2–14.4	13.0
	5–9 y	M+F	11.9–14.4	13.3
	10–18 y	M+F	12.1–14.6	13.5
Thrombin time (sec.)	Fetuses				Fetuses: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Diagnostica Stago coagulation test. Samples of 22 children were investigated in the age groups. Lit. /31/
	19–23 w	M+F	22–44	34.2
	24–29 w	M+F	24–28	26.2
	30–38 w	M+F	17–23.3	21.4
	Children				Children and adults: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Organon Technika coagulation test. Samples of 44–77 children were investigated in the age groups. Lit. /32, 33/
	1 d	M+F	19–28.3	23.5
	5 d	M+F	18.0–29.2	23.1
	1 m	M+F	19.4–29.2	24.3
	3 m	M+F	20.5–29.7	25.1
	6 m	M+F	19.8–31.1	25.5
	Adults	M+F	19.7–30.3	25.0
Von Willebrand Factor-Antigen (vWF: Ag) (U/mL)	Children				Children 1 m to 18 y: Interval of 2.5% and 97.5% percentiles. Laboratory investigation was carried out using Siemens BCS/BCT vWF: Ag Kit. Samples of 40–242 children were investigated in the age groups. Lit. /40/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1–3 m	M+F	0.78–1.91	1.43
	4–6 m	M+F	0.65–2.18	1.10
	7–12 m	M+F	0.60–1.57	1.05
	13 m – 4 y	M+F	0.53–1.60	0.89
	5–9 y	M+F	0.57–1.87	0.90
	10–18 y	M+F	0.51–1.93	0.99
Von Willebrand Factor (vWF: RCo) (U/mL)	Children				Children 1 m to 18 y: Interval of 2.5% and 97.5% percentiles. Laboratory investigations were carried out using Siemens BCS/BCT VWF-reagent . Samples of 40–242 children were investigated in the age groups. Lit. /40/ The concentration of pooled plasma of healthy persons is 1.0 U/ml.
	1–3 m	M+F	0.60–2.20	1.36
	4–6 m	M+F	0.52–2.09	1.05
	7–12m	M+F	0.48–1.53	0.96
	13 m – 4 y	M+F	0.43–1.63	0.87
	5–9 y	M+F	0.40–1.97	0.87
	10–18 y	M+F	0.45–1.81	0.89

Table 54-4 Reference intervals and orienting ranges of “normal“ for autoimmune antibodies /41/

Analyt	Age (years)	Sex	95th percentile	97.5th percentile	99th percentile
ACA	1–< 19	F+M	12.2 CU	14.3	15.9
ACA	1–< 6	F+M	15.6 CU	15.9	15.9
ACA	6–< 19	F+M	9.7 IU/ml	12.1	13.0
ds DNA	1–< 19	F+M	15.5 IU/ml	16.5	18.6
Sm	1–< 19	F+M	7.6 CU	14.3	16.9
SSB	1–< 19	F+M	3.3 CU	3.5	3.9
RNP	1–< 19	F+M	3.5 CU	3.5	4.3
Ro 52	1–< 19	F+M	2.3 CU	2.3	2.3
Ro 60	1–< 19	F+M	4.9 CU	4.9	4.9
MPO	1–< 19	F+M	7.8 CU	9.2	12.3
MPO	1–< 11.3	F+M	9.2 CU	11.2	12.6
MPO	11.3–< 19	F+M	5.0 CU	5.4	5.4
PR3	1–< 19	F+M	3.1 CU	8.8	11.8
tTGA	1–< 19	F+M	5.2 CU	7.5	9.7
tTGA	1–< 19	F	5.2 CU	6.3	6.4
tTGA	1–< 19	M	5.4 CU	9.3	10.4
Automated two step chemiluminescent immunoassay using Bio-Flash Analyzer and corresponding reagents (Werfen); ACA, anti-cytoplasmatic Ab; dsDNA, double strain DNA-Ab; SM-Ab, antibodies directed against nuclear antigen Smith; SSB, nuclear antigen; RNP, ribonucleoproteim; Ro, nuclear antigen; MPO, myeloperoxidase Ab; PR3, proteinase3-Ab; tTGA, tissue transglutaminase-Ab; CU, chemiluminescent units; IU, international units
ANA-IFT	1–< 16	F+M	Titer 1 : 40 to 1 : 80

Bestimmung für unterschiedliche Altersbereiche von 1–19 Jahren /41/

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