Biochemical Analysis Plan

Attachment 3. Biochemical Analytical Plan in Children and Adults.

Biochemical analytical plan in children and adults: performing laboratories, reference levels, reporting ranges, clinical guidelines, and critical values.

Laboratory and Contact	Analyte	* CLIA Cert.	Matrix	Volume	NHANES 1 (µg/L) 2013 - 2014
Children and Adults
NCEH/Division of Laboratory Sciences* Contact: Dr. Antonia Calafat	Per- and Poly-fluoroalkyl Substances (PFAS)	Yes	Serum	2 ml (for all PFAS)	Age Group (years):	50th to 95th %
	perfluorooctanoic acid (PFOA)‡				3-5: 6-11: 12-19: 20+:	1.80 – 5.58 1.94 – 3.84 1.67 – 3.47 2.07 – 5.60
	n-PFOA - linear isomer				3-5: 6-11: 12-19: 20+:	1.72 – 5.32 1.84 – 3.77 1.60 – 3.40 2.00 – 5.40
	Sb-PFOA - serum branched isomer				3-5: 6-11: 12-19: 20+:	< LOD – 0.280 < LOD – 0.230 < LOD – 0.200 < LOD – 0.200
	perfluorooctane sulfonic acid, (PFOS)‡				3-5: 6-11: 12-19: 20+:	3.41 – 8.82 4.02 – 12.4 3.60 – 9.30 5.60 – 19.5
	n-PFOS – linear isomer				3-5: 6-11: 12-19: 20+:	2.11 – 6.19 2.65 – 8.41 2.70 – 7.10 3.70 – 15.1
	Sm-PFOS – serum branched				3-5: 6-11: 12-19: 20+:	1.00 – 3.60 1.41 – 4.25 1.00 – 2.30 1.60 – 5.30

Limit of detection (LOD, see Data Analysis section) for Survey year 13-14 is 0.1. < LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample.

¹ CDC. 2018. 2013-2014 NHANES 50^th to 95^th percentiles among children 12-19 years and adults 20+ years old from the Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, March 2018. Accessed April 13, 2018 at (https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume1_Mar2018.pdf).

‡ See Calculation of PFOS and PFOA as the Sum of Isomers for additional information in March 2018 Updated Tables.

Laboratory and Contact	Analyte	* CLIA Cert.	Matrix	Volume	NHANES 1 (µg/L) 2013 - 2014
Children and Adults
NCEH/Division of Laboratory Sciences* Contact: Dr. Antonia Calafat	Per- and Poly-fluoroalkyl Substances (PFAS) (continued)	Yes	Serum	2 ml (for all PFAS)	Age Group (years):	50th to 95th %
	perfluorohexane sulfonic acid (PFHxS)				3-5: 6-11: 12-19: 20+:	0.740 – 1.62 0.850 – 4.14 1.10 – 6.30 1.40 – 5.50
	2-(N-methyl-perfluorooctane sulfonamido) acetic acid (Me-PFOSAA)				3-5: 6-11: 12-19: 20+:	0.110 – 1.02 0.110 – 0.940 0.100 – 0.600 < LOD – 0.600

Limit of detection (LOD, see Data Analysis section) for Survey year 13-14 is 0.1. < LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. ‡ Not measured after Survey Years 2011-2012.

¹ CDC. 2018. 2013-2014 NHANES 50^th to 95^th percentiles among children 12-19 years and adults 20+ years old from the Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, March 2018. Accessed April 13, 2018 at (https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume1_Mar2018.pdf).

Laboratory and Contact	Analyte	* CLIA Cert.	Matrix	Volume	NHANES 1 (µg/L) 2013 - 2014‡‡
Children and Adults
NCEH/Division of Laboratory Sciences* Contact: Dr. Antonia Calafat	Per- and Poly-fluoroalkyl Substances (PFAS) (continued)	Yes	Serum	2 ml (for all PFAS)	Age Group (years):		50th to 95th %
	perfluorononanoic acid (PFNA)				3-5: 6-11: 12-19: 20+:		0.620 – 3.49 0.750 – 3.19 0.500 – 2.00 0.700 – 2.00
	perfluorodecanoic acid (PFDA)				3-5: 6-11: 12-19: 20+:		0.100 – 0.370 < LOD – 0.350 0.100 – 0.400 0.193 – 0.800
	perfluoroundecanoic acid (PFUnDA)				3-5: 6-11: 12-19: 20+:		< LOD – 0.370 < LOD – 0.250 < LOD – 0.200 < LOD – 0.500
Laboratory and Contact	Proposed Biospecimen Bank for Future Analytes	* CLIA Cert.	Matrix	Volume	NHANES TBD (µg/L) 20xx – 20xx
Children and Adults
NCEH/Division of Laboratory Sciences* Contact: Dr. Antonia Calafat	Per- and Poly-fluoroalkyl Substances (PFAS)	Yes	Spot Urine (morning void)	7 ml (for all)	Age Group:	50th to 95th %
	To be determined (TBD) when analytical methods are developed (Including but not limited to the following 18 analytes: PFOA [n-PFOA;, Sb-PFOA], PFOA [n-PFOS, Sm-PFOS], PFHxS, PFBS, PFHpA, PFNA, PFDA, PFUnDA, PFPrS, PFHpS, PFBA, PFPeA, PFHxA, HFPO-DA (GenX), DONA, 9Cl-PF3ONS)				3-5: 6-11: 12-19: 20+:	TBD TBD TBD TBD
	Creatinine (for urinary creatinine correction; may be contracted)				TBD

Limit of detection (LOD, see Data Analysis section) for Survey year 13-14 is 0.1. < LOD means less than the limit of detection, which may vary for some chemicals by year and by individual sample. ‡ Not measured after Survey Years 2011-2012. ‡‡ Reference ranges for NHANES 2017-2018 are listed at https://www.cdc.gov/exposurereport/pfas_early_release.html;

¹ CDC. 2018. 2013-2014 NHANES 50^th to 95^th percentiles among children 12-19 years and adults 20+ years old from the Fourth National Report on Human Exposure to Environmental Chemicals, Updated Tables, March 2018. Accessed April 13, 2018 at (https://www.cdc.gov/exposurereport/pdf/FourthReport_UpdatedTables_Volume1_Mar2018.pdf).

Laboratory and Contact	Analyte	* CLIA Cert.	Matrix	Volume	Reportable Range, Guidelines, Critical Values
Children and Adults
Commercial Laboratory (to be determined)* Contact:	Lipids	Yes	Serum	1 ml (for all)
	Total cholesterol, fasting				Coronary Heart Disease Risk (CHD)1 Adult, 18+ years: Desirable: <200 mg/dL Borderline High: 200-239 mg/dL High: ≥240 mg/dL Child, 2-17 years: Acceptable: <170 mg/dL Borderline high: 170-199 mg/dL High: ≥200 mg/dL
	Triglycerides, fasting				CHD Risk1 Adult, 18+ years: Normal: <150 mg/dL Borderline High: 150-199 mg/dL High: 200-499 mg/dL Very High: ≥500 mg/dL Critical Value: >1,000 mg/dL Child, 2-9 years: Acceptable: <75 mg/dL Borderline high: 75-99 mg/dL High: ≥100 mg/dL Child, 10-17 years: Acceptable: <90 mg/dL Borderline high: 90-129 mg/dL High: > or =130 mg/dL
	Low Density Lipoprotein (LDL), fasting				CHD Risk1 Adult, 18+ years: Desirable: <100 mg/dL Above Desirable: 100-129 mg/dL Borderline high: 130-159 mg/dL High: 160-189 mg/dL Very high: ≥190 mg/dL Child, 2-17 years: Acceptable: <110 mg/dL Borderline high: 110-129 mg/dL High: ≥130 mg/dL
	High Density Lipoprotein (HDL), fasting				CHD Risk1 Adult, 18+ years: Males: ≥40 mg/dL Females: ≥50 mg/dL Child, 2-17 years: Low: <40 mg/dL Borderline low: 40-45 mg/dL Acceptable: > 45 mg/dL

Laboratory and Contact

Analyte

* CLIA Cert.

Matrix

Volume

Reportable Range, Guidelines,

Critical Values

Children and Adults

Commercial Laboratory (to be determined)*

Contact:

Uric Acid

Yes

Serum

1 ml

Males²

≤ 8.0 mg/dL

Females

≤ 6.1 mg/dL

Creatinine (to estimate glomerular filtration rate [eGFR])

Males³

1-2 years: 0.1-0.4 mg/dL

3-4 years: 0.1-0.5 mg/dL

5-9 years: 0.2-0.6 mg/dL

10-11 years: 0.3-0.7 mg/dL

12-13 years: 0.4-0.8 mg/dL

14-15 years: 0.5-0.9 mg/dL

> or =16 years: 0.8-1.3 mg/dL

Reference values have not been established for patients that are <12 months of age.

 

Females

1-3 years: 0.1-0.4 mg/dL

4-5 years: 0.2-0.5 mg/dL

6-8 years: 0.3-0.6 mg/dL

9-15 years: 0.4-0.7 mg/dL

> or =16 years: 0.6-1.1 mg/dL

Reference values have not been established for patients that are <12 months of age.

 

ESTIMATED GFR

>60 mL/min/BSA

Note: eGFR results will not be calculated for patients <18 or >70 years old.

Laboratory and Contact

Analyte

* CLIA Cert.

Matrix

Volume

Reportable Range, Guidelines,

Critical Values

Children and Adults

Commercial Laboratory (to be determined)*

Contact:

Thyroid Hormones

Yes

Serum

1 ml

Thyroid Stimulating Hormone (TSH)

0.30-3.0 mIU/L ⁴

Free Total Thyroxine (Free T4)

0.8-2.0 ng/dL

Total Thyroxine (TT4)

4.5-12.5 µg/dL

Total Triiodothyronine (TT3)

80-180 ng/dL

Commercial Laboratory (to be determined)*

Contact:

Liver Tests

Yes

Serum

2 ml

(for all)

Alanine transaminase (ALT)

15-65 U/L ⁵

Aspartate transaminase (AST)

5-40 U/L

Alkaline phosphatase (ALP)

Female: 50-136 U/L;

Male: 40-136 U/L

Gamma-glutamyltransferase (GGT)

Female 5-55 U/L;

Male 5-85 U/L

Albumin (Alb)

3.4-5.0 g/dL

Critical Value: <1.5 g/dL

Critical Value: >7.9 g/dL

Total bilirubin (TBIL)

0.0 – 1.0 mg/dL

Critical Value: >12.9 mg/dL

Direct bilirubin (Conjugated Bilirubin)

0.0-0.3 mg/dL

Non-alcoholic fatty liver disease (NAFLD)/steatohepatitis

Cytokeratin 18 M30 (CK-18 M30)

Cytokeratin 18 M65 (CK-18 M65)

No evident liver disease: M30 <200 U/L and M65 <300 U/L

TASH: M30<200 U/L and M65 >300 U/L

Other liver disease: M30: >200 U/L

Laboratory and Contact

Analyte

* CLIA Cert.

Matrix

Volume

Reportable Range, Guidelines,

Critical Values

Children and Adults

Commercial Laboratory (to be determined)*

Contact:

Sex Hormones

Yes

Serum

1 ml

Testosterone

Males⁶        

4-9 years: <7-20 ng/dL

10-11 years: <7-130 ng/dL

12-13 years: <7-800 ng/dL

14 years: <7-1,200 ng/dL

15-16 years: 100-1,200 ng/dL

17-18 years: 300-1,200 ng/dL

≥19 years: 240-950 ng/dL      

Females           

4-9 years: <7-20 ng/dL

10-11 years: <7-44 ng/dL

12-16 years: <7-75 ng/dL

17-18 years: 20-75 ng/dL

≥19 years: 8-60 ng/dL

Estradiol

CHILDREN⁷

Males

Tanner Stages	Reference Range
Stage I (>14 days and prepubertal)	<LOD-13 pg/mL
Stage II	<LOD-16 pg/mL
Stage III	<LOD-26 pg/mL
Stage IV	<LOD-38 pg/mL
Stage V	10-40 pg/mL

Females

Tanner Stages	Mean Age	Reference Range
Stage I (>14 days and prepubertal)	7.1 years	Undetectable-20 pg/mL
Stage II	10.5 years	Undetectable-24 pg/mL
Stage III	11.6 years	Undetectable-60 pg/mL
Stage IV	12.3 years	15-85 pg/mL
Stage V	14.5 years	15-350 pg/mL**

ADULTS

Males: 10-40 pg/mL

Females

Premenopausal: 15-350 pg/mL**

Postmenopausal: <10 pg/mL

**E2 levels vary widely through the menstrual cycle.

Sex hormone-binding globulin (SHBG)

CHILDREN⁸

Males

Tanner Stages	Reference Range
Stage I	31-167 nmol/L
Stage II	49-179 nmol/L
Stage III	5.8-182 nmol/L
Stage IV	14-98 nmol/L
Stage V	10-57 nmol/L

Females

Tanner Stages	Reference Range
Stage I	43-197 nmol/L
Stage II	7.7-119 nmol/L
Stage III	31-191 nmol/L
Stage IV	31-166 nmol/L
Stage V	18-144 nmol/L

ADULTS          

Males: 10-57 nmol/L

Females (non-pregnant): 18-144 nmol/L

Follicle stimulating hormone (FSH)

Males⁹

4-6 years: < or =6.7 IU/L

7-8 years: < or =4.1 IU/L

9-10 years: < or =4.5 IU/L

11 years: 0.4-8.9 IU/L

12 years: 0.5-10.5 IU/L

13 years: 0.7-10.8 IU/L

14 years: 0.5-10.5 IU/L

15 years: 0.4-18.5 IU/L

16 years: < or =9.7 IU/L

17 years: 2.2-12.3 IU/L

≥18 years: 1.0-18.0 IU/L

Females

15 days-6 years: < or =3.3 IU/L

7-8 years: < or =11.1 IU/L

9-10 years: 0.4-6.9 IU/L

11 years: 0.4-9.0 IU/L

12 years: 1.0-17.2 IU/L

13 years: 1.8-9.9 IU/L

14-16 years: 0.9-12.4 IU/L

17 years: 1.2-9.6 IU/L

≥18 years:

Premenopausal

Follicular: 3.9-8.8 IU/L

Midcycle: 4.5-22.5 IU/L

Luteal: 1.8-5.1 IU/L

Postmenopausal: 16.7-113.6 IU/L

Insulin-like growth factor (IGF-1)

Laboratory and Contact	Analyte	* CLIA Cert.	Matrix		Volume		Reportable Range, Guidelines, Critical Values
Children and Adults
Commercial Laboratory (to be determined)* Contact:	Immune Function	Yes	Serum		1 ml
	Ig A, Ig G, Ig M, Ig E
Commercial Laboratory (to be determined)* Contact:	Glycemic Parameters	Yes
	Glycosylated hemoglobin (HbA1c)		Whole Blood EDTA		2 ml		Diabetes Risk10 Normal: <5.7% Increased Risk Diabetes: 5.7-6.4% Diabetes: ≥6.5% (confirmation required)
	Glucose, fasting, 8-hour		Serum		2 ml (for all four)
	Insulin						<17 µU/ml 8
	Glutamate Decarboxylase -65 (Anti-GAD 65)						Negative Antibody: DK≤33 8 Positive Antibody: DK>33
	Thyrosine Phosphatase-like Protein Autoantibodies (Anti-IA2)						Negative Antibody: DK<5 8 Positive Antibody: DK≥5
Children Only
Commercial Laboratory (to be determined)* Contact:	Antibodies to measles, mumps, rubella, tetanus, and diphtheria	Yes		Serum		1 ml
Child Total						Serum - 11ml Whole Blood – 2 ml Urine – 7 ml Red Top 20 ml EDTA Lavender Top 3 ml

Adults Only
Commercial Laboratory (to be determined)* Contact:	Autoimmune Parameters	Yes	Serum	2 ml (for all)
	Rheumatoid Factor (RF)				< 15 IU/mL11
	Antinuclear Antibody (ANA) screen				< or =1.0 U (negative)12 1.1-2.9 U (weakly positive) 3.0-5.9 U (positive) > or =6.0 U (strongly positive)
	Antinuclear Antibody (ANA) titer
Adult Total				Serum - 13ml Whole Blood – 2 ml Urine – 7 ml Red Top 30 ml EDTA Lavender Top 3 ml

1 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8320

2 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8440

3 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8472

4 University of Southern California Clinical Laboratories Endocrine Services.

5 University of Louisville Department of Medicine, Gastroenterology (updated 14 October 2015).

6 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/83686

7 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/81816

8 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9285

9 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8670

10 American Diabetes Association. Standards of Medical Care in Diabetes - 2011. Diabetes Care. January 2011;34(Supplement 1):S11-S61 (subject to periodic update).

11 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9060

12 https://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9026