EXPRESS: Method dependent variation in TSH and FT4 reference intervals in pregnancy: a systematic review

2021 ◽  
pp. 000456322110269
Author(s):  
O E Okosieme ◽  
Medha Agrawal ◽  
Danyal Usman ◽  
Carol Evans
Keyword(s):  
Systematic Review ◽  
Reference Interval ◽  
First Trimester ◽  
Reference Intervals ◽  
Assay Method ◽  
Specific Reference ◽  
Upper Limits ◽  
Wide Range ◽  
Assay Methods ◽  
In Pregnancy

Background: Gestational TSH and FT4 reference intervals may differ according to assay method but the extent of variation is unclear and has not been systematically evaluated. We conducted a systematic review of published studies on TSH and FT4 reference intervals in pregnancy. Our aim was to quantify method-related differences in gestation reference intervals, across four commonly used assay methods, Abbott, Beckman, Roche, and Siemens. Methods: We searched the literature for relevant studies, published between January 2000 and December 2020, in healthy pregnant women without thyroid antibodies or disease. For each study, we extracted trimester-specific reference intervals (2.5–97.5 percentiles) for TSH and FT4 as well as the manufacturer provided reference interval for the corresponding non-pregnant population. Results: TSH reference intervals showed a wide range of study-to-study differences with upper limits ranging from 2.33 to 8.30 mU/L. FT4 lower limits ranged from 4.40–13.93 pmol/L, with consistently lower reference intervals observed with the Beckman method. Differences between non-pregnant and first trimester reference intervals were highly variable, and for most studies the TSH upper limit in the first trimester could not be predicted or extrapolated from non-pregnant values. Conclusions: Our study confirms significant intra and inter-method disparities in gestational thyroid hormone reference intervals. The relationship between pregnant and non-pregnant values is inconsistent and does not support the existing practice in some laboratories of extrapolating gestation references from non-pregnant values. Laboratories should invest in deriving method-specific gestation reference intervals for their population.

Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays

2021 ◽  
Author(s):  
K Aaron Geno ◽  
Matthew S Reed ◽  
Mark A Cervinski ◽  
Robert D Nerenz
Keyword(s):  
Pregnant Women ◽  
Equilibrium Dialysis ◽  
Reference Interval ◽  
First Trimester ◽  
Reference Intervals ◽  
Free Thyroxine ◽  
Specific Reference ◽  
Childbearing Age ◽  
Thyroid Autoantibody ◽  
The Impact

Abstract Introduction Automated free thyroxine (FT4) immunoassays are widely available, but professional guidelines discourage their use in pregnant women due to theoretical under-recoveries attributed to increased thyroid hormone binding capacity and instead advocate the use of total T4 (TT4) or free thyroxine index (FTI). The impact of this recommendation on the classification of thyroid status in apparently euthyroid pregnant patients was evaluated. Methods After excluding specimens with thyroid autoantibody concentrations above reference limits, thyroid-stimulating hormone (TSH), FT4, TT4, and T-uptake were measured on the Roche Cobas® platform in remnant clinical specimens from at least 147 nonpregnant women of childbearing age and pregnant women at each trimester. Split-sample comparisons of FT4 as measured by the Cobas and equilibrium dialysis were performed. Results FT4 decreased with advancing gestational age by both immunoassay and equilibrium dialysis. TSH declined during the first trimester, remained constant in the second, and increased throughout the third, peaking just before delivery. Interpretation of TT4 concentrations using 1.5-times the nonpregnant reference interval classified 13.6% of first trimester specimens below the lower reference limit despite TSH concentrations within trimester-specific reference intervals. Five FTI results from 480 pregnant individuals (about 1.0%) fell outside the manufacturer’s reference interval. Conclusions Indirect FT4 immunoassay results interpreted in the context of trimester-specific reference intervals provide a practical and viable alternative to TT4 or FTI. Declining FT4 and increasing TSH concentrations near term suggest that declining FT4 is not an analytical artifact but represents a true physiological change in preparation for labor and delivery.

scholarly journals Pregnancy-specific reference intervals for BNP and NT-pro BNP – changes in natriuretic peptides related to pregnancy

2021 ◽  
Author(s):  
Samuel Dockree ◽  
Jennifer Brook ◽  
Brian Shine ◽  
Tim James ◽  
Manu Vatish
Keyword(s):  
Pregnant Women ◽  
Natriuretic Peptides ◽  
First Trimester ◽  
Reference Intervals ◽  
Cardiac Biomarkers ◽  
Specific Reference ◽  
Third Trimester ◽  
The Third ◽  
Cardiac Strain ◽  
In Pregnancy

Abstract Background Cardiac disease is the leading cause of maternal mortality in the UK, so accurate cardiovascular diagnoses in pregnancy are essential. BNP (B-type natriuretic peptide) and NT-pro BNP (N-terminal-pro BNP) are useful clinical tools for investigating suspected peripartum cardiomyopathy but, as the pregnancy-specific reference intervals are undefined, it is uncertain how they should be interpreted in pregnant women. Methods Longitudinal study of 260 healthy pregnant women, with sampling in each trimester to define 95% reference intervals. Results The upper reference limit for NT-pro BNP was 200 pg/mL in the first and second trimesters, and 150 pg/mL in the third. Levels were significantly reduced in overweight women in the third trimester (p=0.0001), which supports the partitioning of reference intervals by BMI. The upper limit for BNP was 50 pg/mL, with no detectable trimester-related differences. Whilst other biomarkers (haemoglobin and platelets) fell throughout pregnancy, both natriuretic peptides were initially elevated before falling by the third trimester, suggesting that the observed changes in natriuretic peptides are driven by dynamic interplay between cardiac strain and progressive haemodilution. NT-pro BNP in the first trimester was inversely associated with neonatal birthweight at term (p=0.011). Conclusions Cardiac biomarkers have an important role for investigating suspected disease in high-risk pregnant women, but a robust assessment of the levels expected in healthy pregnant women is an essential prerequisite to their application in clinical practice. This study has defined trimester- and BMI-specific reference intervals for NT-pro BNP and BNP, which may improve how women with suspected cardiovascular disease are investigated in pregnancy.

Pediatric reference intervals for 1,25-dihydroxyvitamin D using the DiaSorin LIAISON XL assay in the healthy CALIPER cohort

2018 ◽  
Vol 56 (6) ◽  
pp. 964-972 ◽  
Author(s):  
Victoria Higgins ◽  
Dorothy Truong ◽  
Nicole M.A. White-Al Habeeb ◽  
Angela W.S. Fung ◽  
Barry Hoffman ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Critical Role ◽  
Reference Interval ◽  
Reference Intervals ◽  
Biologically Active ◽  
Specific Reference ◽  
Healthy Children ◽  
Serum Samples ◽  
Dihydroxyvitamin D ◽  
1,25 Dihydroxyvitamin D

Abstract Background: 1,25-dihydroxyvitamin D (1,25(OH)2D), the biologically active vitamin D metabolite, plays a critical role in calcium and phosphate homeostasis. 1,25(OH)2D is measured to assess calcium and phosphate metabolism, particularly during periods of profound growth and development. Despite its importance, no reliable pediatric reference interval exists, with those available developed using adult populations or out-dated methodologies. Using the fully automated chemiluminescence immunoassay by DiaSorin, we established 1,25(OH)2D pediatric reference intervals using healthy children and adolescents from the CALIPER cohort. Methods: Serum samples from healthy subjects (0 to <19 years) were analyzed for 1,25(OH)2D using the DiaSorin LIAISON XL assay and age-specific reference intervals were established. The Mann-Whitney U-test was used to determine seasonal differences. Pooled neonatal and infantile samples were quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS) to determine if elevated concentrations during the first year of life may be attributed to cross-reacting moieties. Results: Three reference interval age partitions were required with highest levels in subjects 0 to <1 year (77–471 pmol/L), which declined and narrowed after 1 year (113–363 pmol/L) and plateaued at 3 years (108–246 pmol/L). 1,25(OH)2D concentration was not significantly affected by seasonal variation or sex. Elevated 1,25(OH)2D concentrations in neonatal and infantile samples may be the result of an interfering substance. The absence of 3-epi-1,25-dihydroxyvitamin D in the pooled samples makes it unlikely to be the interfering moiety. Conclusions: Pediatric reference intervals for 1,25(OH)2D were established to improve test result interpretation in children and adolescents. 1,25(OH)2D is elevated in a proportion of neonates and infants, which may be the result of a cross-reacting moiety.

Distribution of HOMA-IR in a population-based cohort and proposal for reference intervals

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Bassel Matli ◽  
Andreas Schulz ◽  
Thomas Koeck ◽  
Tanja Falter ◽  
Johannes Lotz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fasting Glucose ◽  
Reference Group ◽  
Reference Interval ◽  
Population Based ◽  
Reference Intervals ◽  
Health Study ◽  
Specific Reference ◽  
Model Assessment ◽  
Significant Difference

Abstract Objectives Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35–74 years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteria. Age- and sex-dependent distributions of HOMA-IR and reference intervals were obtained. In a substudy three insulin assays were compared and HOMA-IR estimated for each assay. Results Among the 10,340 participants analyzed there were 6,590 non-diabetic, 2,901 prediabetic, and 849 diabetic individuals. Median (interquartile range [IQR]) HOMA-IR was 1.54 (1.13/2.19), 2.00 (1.39/2.99), and 4.00 (2.52/6.51), respectively. The most stringently selected reference group consisted of 1,065 persons. Median (IQR) HOMA-IR was 1.09 (0.85/1.42) with no significant difference between men and women. The 97.5th percentile was 2.35. There was a non-significant trend towards higher values with older age. Comparison of three immunoassays for insulin showed an unsatisfactory correlation among the assays and systematic differences in calculated HOMA-IR. Conclusions We present HOMA-IR reference intervals for adults derived by more or less stringent selection criteria for the reference cohort. In addition we show that assay specific reference intervals for HOMA-IR are required.

scholarly journals SUN-222 Pre- and Post-Pubertal Reference Ranges for Oxygenated Androgens in Saliva

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Joanne Adaway ◽  
Graeme Eisenhofer ◽  
Angela Huebner ◽  
Nils Krone ◽  
Malcolm McTaggart ◽  
...  
Keyword(s):  
Reference Interval ◽  
Reference Intervals ◽  
Range Data ◽  
Reference Ranges ◽  
Non Invasive ◽  
Premature Adrenarche ◽  
Upper Limits ◽  
Males And Females ◽  
Monitoring Treatment ◽  
Ovarian Syndrome

Abstract Oxygenated androgens such as 11 β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) contribute significantly to the androgen pool in humans and their measurement has been shown to be useful in diagnosing disorders such as polycystic ovarian syndrome or premature adrenarche and also in monitoring treatment of congenital adrenal hyperplasia, alongside the classical androgens. Their measurement in saliva is particularly advantageous due to the non-invasive nature of sampling, meaning samples can easily be taken regularly to monitor treatment; however reference range data is not currently available for 11OHA4 and 11KT, limiting their clinical use. These analytes were measured in saliva samples from pre and post-pubertal males and females to inform reference ranges for these analytes. Samples collected into salivettes as part of the PRIMMS study (Technische Universität Dresden) were used for this work. A total of 130 samples (35 from pre-pubertal females, 43 from post-pubertal females, 42 from pre-pubertal males and 20 from post-pubertal males) were analysed for 11OHA4 and 11KT by LC-MS/MS. The ages of the participants ranged from 3.77 to 14.0 years in the pre-pubertal samples and 13.9-17.9 years in the post-pubertal samples. Pubertal status was determined clinically. The upper cut-off of the reference interval for 11OHA4 was 560 pmol/L in pre-pubertal females and 590 pmol/L in males, whilst 11KT had an upper limit of 216 pmol/L in females and 205 pmol/L in males. The upper limits of the ranges were higher in post-pubertal samples, with ranges of up to 1542 pmol/L in females and 1775 pmol/L in males for 11OHA4; the ranges for 11KT were up to 654 pmol/L for post pubertal females and 585 pmol/L for post-pubertal males. The data shows, as expected, a rise in the 11 oxygenated androgens post puberty. The upper limits of reference intervals for both analytes were very similar in males and females both pre- and post pubertally. These data can be used to inform clinical interpretation of the 11-oxygenated androgens; further work is required with larger cohorts of samples to develop more robust reference ranges.

scholarly journals Early pregnancy reference intervals; 29 serum analytes from 4 to 12 weeks’ gestation in naturally conceived and uncomplicated pregnancies resulting in live births

2019 ◽  
Vol 57 (12) ◽  
pp. 1956-1967 ◽  
Author(s):  
Jesper Friis Petersen ◽  
Lennart J. Friis-Hansen ◽  
Andreas Kryger Jensen ◽  
Anders Nyboe Andersen ◽  
Ellen C.L. Løkkegaard
Keyword(s):  
Pregnant Women ◽  
Early Pregnancy ◽  
Clinical Chemistry ◽  
Clinical Care ◽  
Local Population ◽  
First Trimester ◽  
Reference Intervals ◽  
Specific Reference ◽  
Cancer Antigen 125 ◽  
Serum Samples

Abstract Background Pregnancy introduces major physiological changes that also alter biochemical analytes. Maternal and perinatal health can be optimized by early intervention and therefore, pregnancy-specific reference intervals (RIs) for the local population are warranted. While the second and third trimester-specific changes are well described, the first trimester is less well characterized. We therefore wanted to facilitate early detection of abnormalities by generating first trimester reference values for 29 common analytes. Methods In a prospective early pregnancy (PEP) cohort (2016–2017), 203 pregnant women were recruited from 4 to 8 weeks’ gestation. Consecutive blood samples were drawn every 2 weeks until an ongoing second trimester pregnancy (n = 164) or a miscarriage (n = 39) occurred. After exclusion of women with complicated pregnancies or deliveries (n = 42), 122 women were included. The serum samples collected at <6, 6–8, 8–10, 10–12 and >12 weeks’ gestation were analyzed for 29 common analytes. Subsequently the RIs were calculated according to the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) recommendations (2.5–97.5th percentiles) and compared with the conventional RIs for non-pregnant women. Results Human chorionic gonadotropin (hCG), progesterone (P4), estradiol (E2), pregnancy-associated plasma protein A (PAPP-A), cancer antigen 125 (CA125), thyroid stimulating hormone (TSH), creatinine (CREA) and albumin (ALB) showed an early pregnancy-dependent change compared with conventional limits. For ALB the change was seen at 5.5 weeks’ gestation. Conclusions We report gestational age-specific RIs available from the early part of the first trimester applicable to everyday clinical care of pregnant women. Well-known alterations of RIs seen in later trimesters are also observed in the first.

Gestational age-specific reference intervals for 15 biochemical measurands during normal pregnancy in China

2017 ◽  
Vol 55 (4) ◽  
pp. 446-452 ◽  
Author(s):  
Yanpeng Dai ◽  
Junjie Liu ◽  
Enwu Yuan ◽  
Yushan Li ◽  
Quanxian Wang ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Gestational Age ◽  
Parametric Method ◽  
First Trimester ◽  
Normal Pregnancy ◽  
Reference Intervals ◽  
Specific Reference ◽  
Gamma Glutamyl Transpeptidase ◽  
Cross Sectional ◽  
Laboratory Results

Aims Physiological changes that occur during pregnancy can influence biochemical parameters. Therefore, using reference intervals based on specimens from non-pregnant women to interpret laboratory results during pregnancy may be inappropriate. This study aimed to establish the essential reference intervals for a range of analytes during pregnancy. Methods A cross-sectional study was performed in 13,656 healthy pregnant and 2634 non-pregnant women. Fifteen biochemical measurands relating to renal and hepatic function were analysed using an Olympus AU5400 analyzer (Olympus, Tokyo, Japan). All the laboratory results were checked for outliers using Dixon’s test. Reference intervals were established using a non-parametric method. Results Alanine aminotransferase, aspartate aminotransferase, albumin, cholinesterase, creatinine, direct bilirubin, gamma-glutamyl transpeptidase, total bilirubin, total bile acid and total protein showed a decrease during the whole gestational period, while alkaline phosphatase and uric acid increased. Urea nitrogen, β2-microglobulin and cystatin-C fell significantly during the first trimester and then remained relatively stable until third trimester. Reference intervals of all the measurands during normal pregnancy have been established. Conclusions The reference intervals established here can be adopted in other clinical laboratories after appropriate validation. We verified the importance, for some measurands, of partitioning by gestational age when establishing reference intervals during pregnancy.

Gestation specific reference intervals for thyroid function tests in pregnancy

2016 ◽  
Vol 54 (8) ◽  
Author(s):  
Süleyman Akarsu ◽  
Filiz Akbiyik ◽  
Eda Karaismailoglu ◽  
Zeliha Gunnur Dikmen
Keyword(s):  
Pregnant Women ◽  
Thyroid Function ◽  
First Trimester ◽  
Reference Intervals ◽  
Specific Reference ◽  
Thyroid Function Tests ◽  
Second Trimester ◽  
Third Trimester ◽  
The Third ◽  
Function Tests

AbstractThyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women.Serum samples were collected from 220 non-pregnant women (age: 18–48), and 2460 pregnant women (age: 18–45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer.GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49–2.33 mIU/L, 10.30–18.11 pmol/L and 3.80–5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51–3.44 mIU/L, 10.30–18.15 pmol/L and 3.69–5.90 pmol/L. GRIs for third trimester pregnancies were 0.58–4.31 mIU/L, 10.30–17.89 pmol/L and 3.67–5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals.TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.

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