Continuous reference intervals for holotranscobalamin, homocysteine and folate in a healthy paediatric cohort

Joel D Smith1, Vasiliki Karlaftis2,3, Stephen Hearps2

  • 1Department of Laboratory Services, The Royal Children's Hospital, Parkville, VIC, Australia.

PubMed

Insights

Establishing reference intervals for vitamin B12 and folate markers in children is crucial. This study provides continuous reference intervals for holotranscobalamin, homocysteine, and red cell folate in healthy children aged 30 days to 18 years.

Area of Science:

  • Pediatric Nutrition
  • Clinical Biochemistry
  • Developmental Pediatrics

Background:

  • Vitamin B12 and folate deficiencies are significant concerns in pediatric populations.
  • Accurate reference intervals (RIs) for assessing vitamin B12 and folate metabolism in healthy children are limited.
  • Understanding age-related changes in these markers is essential for proper diagnosis.

Purpose of the Study:

  • To establish continuous, age-specific reference intervals for key vitamin B12 and folate metabolites in children.
  • To characterize the dynamic changes in holotranscobalamin, homocysteine, and red cell folate levels throughout childhood and adolescence.
  • To provide clinicians with reliable data for assessing vitamin B12 and folate status in pediatric patients.

Main Methods:

  • Analysis of blood samples from 378 healthy children aged 30 days to under 18 years.
  • Derivation of continuous 95th percentile reference intervals for holotranscobalamin, homocysteine, and red cell folate.
  • Longitudinal assessment of marker concentrations across different developmental stages.

Main Results:

  • Holotranscobalamin levels were lowest at birth, increased in early childhood, and decreased after ages 4-6 years.
  • Red cell folate levels were highest in early life, declining steadily into adulthood.
  • Total homocysteine levels were elevated in infancy, reached a minimum at age 2, and then increased towards adulthood.

Conclusions:

  • Continuous 95th percentile reference intervals for holotranscobalamin, homocysteine, and red cell folate were successfully established for children aged 30 days to <18 years.
  • These markers exhibit significant dynamic changes during childhood and adolescence.
  • The established RIs will aid clinicians in the accurate assessment of vitamin B12 and folate status in children and adolescents.
Abstract

Related Concept Videos

Bioavailability Study Design: Healthy Subjects Versus Patients01:15

Bioavailability Study Design: Healthy Subjects Versus Patients

Bioavailability studies are essential for evaluating a drug's therapeutic efficacy and understanding its absorption patterns under various physiological conditions. Conducting such studies on target patient populations provides more relevant data by simulating real-world disease states. However, practical challenges often necessitate the use of young, healthy adult volunteers as study subjects.Patients may exhibit altered drug absorption patterns due to the effects of the disease itself,...
Drug Dosing: Infants and Children01:29

Drug Dosing: Infants and Children

Pediatric patient dosages diverge from adults due to disparities in body surface area, total body water, and extracellular fluid per kilogram of body weight. The dosing regimen considers the variations in pharmacokinetics and pharmacology across distinct age groups, encompassing preterm newborns, infants, young children, older children, and adolescents. Calculation of pediatric patient doses is predicated on determining body surface area, which exhibits a superior correlation with the child's...
Pharmacokinetics in Pediatric Patients: Drug Distribution01:17

Pharmacokinetics in Pediatric Patients: Drug Distribution

Drug distribution in the pediatric population exhibits unique challenges and considerations due to the physiological differences between children, particularly neonates and infants, and adults. A crucial aspect of pediatric pharmacology is understanding how these differences impact the pharmacokinetics of various drugs, necessitating age-specific dosing strategies to ensure efficacy and safety.Neonates and infants have a higher total body water content, ~75%–90% of their body weight, compared...
Pharmacokinetics in Pediatric Patients: Drug Metabolism01:24

Pharmacokinetics in Pediatric Patients: Drug Metabolism

In pediatric care, understanding the nuances of hepatic drug metabolism is crucial, as it significantly differs from that of adults. This divergence is primarily due to the developmental stage of drug-metabolizing enzymes, which affects how medications are processed in the body. In neonates, for instance, the activity of Phase I enzymes—critical for the initial breakdown of drugs—is markedly reduced, functioning at just 20–40% of the levels seen in adults. This reduction poses a challenge in...
Pharmacokinetics in Pediatric Patients: Drug Excretion01:26

Pharmacokinetics in Pediatric Patients: Drug Excretion

In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...
Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers01:19

Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers

Cardiac biomarkers are critical in diagnosing, prognosing, and managing cardiovascular diseases. Routine measurement of specific biomarkers such as B-type natriuretic peptide (BNP), C-reactive protein (CRP), and homocysteine (Hcy) is common practice in clinical settings to evaluate heart function and predict cardiovascular events.
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...