Laboratory reference intervals in the assessment of iron status in young children

Parkin, Patricia C.; Hamid, Jemila S.; Borkhoff, Cornelia M.; Abdullah, Kawsari; Atenafu, Eshetu G.; Birken, Catherine S.; Maguire, Jonathon L.; Azad, Azar; Higgins, Victoria; Adeli, Khosrow

doi:10.1136/bmjpo-2017-000074

Cited by 23 publications

(32 citation statements)

References 22 publications

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“…The most common CBC abnormality was mild leukopenia (9/45; 20%). Ferritin deficiency and vitamin D deficiency were frequently noted in the cohort, but are both relatively frequent in the normal pediatric population (Parkin et al 2017; Yesiltepe and Hatun 2018). In the total cohort, 11% had elevated thyroperoxidase antibodies (anti-TPO) and 5% had elevated transglutaminase antibodies, indicating thyroid and celiac disease, respectively.…”

Section: Resultsmentioning

confidence: 99%

Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet

Gromark

Harris

Wickström

et al. 2019

Journal of Child and Adolescent Psychopharmacology

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Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) is a descriptive clinical entity defined by the abrupt onset of psychiatric and somatic symptoms leading to significant loss of function. Data on well-characterized PANS patients are limited, biomarkers have yet to be identified, and a solid evidence base to guide treatment is lacking. In this study, we present our experience of a systematic evaluation of the first 45 patients included in a Swedish cohort.Methods: During the period 2014–2018, our clinic received 100 referrals regarding suspected PANS. All patients underwent a standardized psychiatric/medical evaluation by a child/adolescent psychiatrist and a clinical psychologist or a nurse. Those with severe symptoms were also assessed by a pediatric neurologist and a pediatric rheumatologist. Laboratory tests were obtained at different time points in an attempt to capture an active disease state.Results: Of the 100 referrals, 45 met strict PANS criteria and consented to participate in a long-term follow-up study. The median age at intake was 7.2 years (range 3.0–13.1) and 56% were male. Ninety-three percent fulfilled both criteria for acute/atypical onset of PANS symptoms and having had an infection in relation to onset. Sixteen percent had an onset of an autoimmune or inflammatory disorder in temporal relation to the onset of PANS-related symptoms. The most common onset symptoms were obsessive-compulsive disorder (89%), anxiety (78%), and emotional lability (71%). Twenty-four percent had a preexisting autoimmune disease (AD) and 18% a preexisting psychiatric/neuropsychiatric diagnosis. Sixty-four percent of biological relatives had at least one psychiatric disorder and 76% at least one AD or inflammatory disorder. Complement activation (37%), leukopenia (20%), positive antinuclear antibodies (17%), and elevated thyroid antibodies (11%) were the most common laboratory findings.Conclusions: In our PANS cohort, there was a strong indication of an association with AD. Further work is needed to establish whether any of the potential biomarkers identified will be clinically useful. Long-term follow-up of these patients using the Swedish national registers will enable a deeper understanding of the course of this patient group.

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Section: Resultsmentioning

confidence: 99%

Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet

Gromark

Harris

Wickström

et al. 2019

Journal of Child and Adolescent Psychopharmacology

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“…However, this decision limit for the patient less than 1 year old has been questioned [6]. Importantly, is not based on clinical outcomes as required for establishing a high quality clinical decision limit [7]. Also, since it is difficult to achieve a sufficiently large number of blood samples from healthy infant subjects < 1 year, it has been estimated by extrapolating data from older age groups, thereby not reflecting the different phases of physiological development during infancy [6].…”

Section: Introductionmentioning

confidence: 99%

When age really matters; ferritin reference intervals during infancy revisited

Larsson

Hillarp

Hellström‐Westas

et al. 2019

Scandinavian Journal of Clinical and Laboratory Investigation

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Infants are at risk for iron deficiency. Despite research advances, assessing iron stores during infancy remains a challenge to the clinician. Ferritin is the first-choice laboratory marker for measuring iron stores but it is today still unclear how to evaluate reference intervals among infants. We have studied Swedish infants (n ¼ 456), born at term after normal pregnancies. Ferritin was measured at birth (umbilical cord sample), 48-72 h, 4 months and 12 months. Lower and upper reference interval limits were constructed as the 2.5th and 97.5th percentiles. By a large study population, we were able to use more stringent measures to avoid interference from the acute phase response than previous reports on ferritin reference intervals. When we used mathematical transformation we furthermore avoided potential information loss in precision and confirmed earlier reports of sex differences. At the lower reference interval limits there were small differences between sexes. For the higher limits, the differences were more pronounced in the older infant. At 0-3 d of age we observed a difference between the sexes of only 5% at the upper limits. The differences peaked at 12 months, where the boys' upper 97.5th percentile was 56% compared to girls.

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“…We have previously described reference intervals for hemoglobin and serum ferritin following the Clinical and Laboratory Standards Institute guidelines and found that ∼10% of children 1 to 3 years of age were misclassified (underestimated) by using the lower limit of the reference intervals rather than the currently recommended AAP cutoff values for hemoglobin and serum ferritin. 40 We have also examined the relationship between serum ferritin and hemoglobin in this age group and found that a serum ferritin cutoff of 18 to 24 μg/L corresponds to the point at which hemoglobin plateaus at ∼120 g/L. 41 Strengths of our study include the large sample size of 1735 children attending health supervision visits, with data collected prospectively from several primary care practices where screening for iron deficiency is not current standard of practice.…”

Section: Discussionmentioning

confidence: 99%

Screening for Iron Deficiency in Early Childhood Using Serum Ferritin in the Primary Care Setting

Oatley¹,

Borkhoff

Chen

et al. 2018

Pediatrics

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on behalf of the TARGet Kids! Collaboration OBJECTIVES: The American Academy of Pediatrics recommends universal screening for anemia using hemoglobin at 12 months. However, hemoglobin lacks diagnostic accuracy for iron deficiency, and the optimal age for screening has not been determined. Our objective was to assess a screening strategy for iron deficiency using serum ferritin. METHODS: We conducted a cross-sectional study of children 1 to 3 years old attending a health supervision visit. We examined the relationship between child age and serum ferritin, age and hemoglobin, hemoglobin and serum ferritin, and the prevalence of elevated C-reactive protein (CRP). RESULTS: Restricted cubic spline analysis (n = 1735) revealed a nonlinear relationship between age and serum ferritin (P < .0001). A linear spline model revealed that from 12 to 15 months, for each 1-month increase in age, serum ferritin levels decreased by 9% (95% confidence interval [CI]: 5 to 13). From 15 to 24 months, the rate of change was nonsignificant. From 24 to 38 months, for each month increase in age, serum ferritin increased by 2% (95% CI: 1 to 2). For hemoglobin, from 12 to 24 months, the rate of change was nonsignificant. From 24 to 38 months, for each 1-month increase in age, hemoglobin increased by 20% (95% CI: 9 to 32). Compared with the serum ferritin cutoff of <12 μg/L, the hemoglobin cutoff of <110 g/L had a sensitivity of 25% (95% CI: 19 to 32) and a specificity of 89% (95% CI: 87 to 91). Elevated CRP ≥10 mg/L occurred in 3.3% (95% CI: 2.5 to 4.2). CONCLUSIONS: Screening for iron deficiency using serum ferritin at 15 or 18 months may be a promising strategy. For children at low risk for acute inflammation, concurrent measurement of CRP may not be necessary.

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Laboratory reference intervals in the assessment of iron status in young children

Cited by 23 publications

References 22 publications

Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet

Establishing a Pediatric Acute-Onset Neuropsychiatric Syndrome Clinic: Baseline Clinical Features of the Pediatric Acute-Onset Neuropsychiatric Syndrome Cohort at Karolinska Institutet

When age really matters; ferritin reference intervals during infancy revisited

Screening for Iron Deficiency in Early Childhood Using Serum Ferritin in the Primary Care Setting

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