Trimester-Specific Reference Ranges for Saturated, Monounsaturated and Polyunsaturated Fatty Acids in Serum of Pregnant Women: A Cohort Study from the ECLIPSES Group

In the course of pregnancy, increasing importance is being placed on maintaining optimal fatty acid (FA) levels and particularly n-3 PUFAs to ensure correct fetal development. However, reference ranges for FA have been reported in only a few studies. Our objective is to provide quantitative reference intervals for SFAs, MUFAs, and PUFAs (n-6 and n-3) in a large population of healthy pregnant women from a developed country. A prospective study of pregnant women (n = 479) was conducted from the first trimester (T1) to the third trimester (T3). A total of 11 fatty acids were analyzed in serum by gas chromatography mass spectrometry and were expressed as absolute (µmol/L) and relative (percentage of total FA) concentration units. Serum concentrations of SFAs, MUFAs, n-6 PUFAs, n-3 PUFAs, various FA ratios, and the EFA index were determined. The reference intervals (2.5/97.5 percentiles) in absolute values from T1 ranged from 1884.32 to 8802.81 µmol/L for SFAs, from 959.91 to 2979.46 µmol/L for MUFAs, from 2325.77 to 7735.74 µmol/L for n-6 PUFAs, and from 129.01 to 495.58 µmol/L for n-3 PUFAs. These intervals mainly include the values of other studies from European populations. However, reference ranges vary according to some maternal factors. The FA levels proposed, obtained from a large sample of pregnant women, will be a useful tool for assessing the degree of adequacy of FAs in pregnant women and will help to carry out dietary interventions based on certain maternal factors.

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Reference Intervals for Thyroid Hormones During the First Trimester of Gestation: A Report from an Area with a Sufficient Iodine Level

Hormone and Metabolic Research ◽

10.1055/a-0855-7128 ◽

2019 ◽

Vol 51 (03) ◽

pp. 165-171

Author(s):

Maryam Kianpour ◽

Ashraf Aminorroaya ◽

Massoud Amini ◽

Awat Feizi ◽

Mohsen Janghorbani ◽

...

Keyword(s):

Pregnant Women ◽

First Trimester ◽

Reference Intervals ◽

Specific Reference ◽

Thyroid Peroxidase ◽

Urinary Iodine Concentration ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Iodine Level ◽

First Trimester Of Pregnancy

AbstractThe physiological changes during pregnancy modulate the endocrine system. Therefore, both the American and the European thyroid associations recommend the use of local trimester-specific reference intervals. The purpose of this study was to establish the first trimester reference intervals for thyroid function tests in the central area of Iran. We examined 436 pregnant women in their first trimester of pregnancy, and 444 non-pregnant women in a cross sectional study. Serum levels of thyroid stimulating hormone (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroid peroxidase antibody, urinary iodine concentration (UIC), and thyroid volume were measured for all subjects. The first trimester-specific reference intervals (2.5th–97.5th percentile) were determined for 185 pregnant women and 256 non-pregnant women with negative TPOAb, adequate iodine level (UIC≥150 μg/l in pregnant and UIC≥100 μg/l in non-pregnant women), and normal thyroid examination. We calculated multiples of the median (MoM) for TFTs to normalize the obtained data. The first trimester-specific reference intervals of serum TSH, FT4, and FT3 for pregnant women were 0.20–4.60 mIU/l, 9.0–18.02 pmol/l, and 3.40–5.64 pmol/l, respectively, while the corresponding figures for non-pregnant women were 0.59–5.60 mIU/l, 9.52–19.30 pmol/l, and 3.70–5.55 pmol/l, respectively. The first and 99th percentile MoM of TSH in pregnant women in their first-trimester was 0.06–4.62. The local normal reference ranges for the first trimester of pregnancy in central region of Iran were different from the ranges suggested by the ATA.

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Evaluation of Thyroid Function in Pregnant Women Using Automated Immunoassays

Clinical Chemistry ◽

10.1093/clinchem/hvab009 ◽

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.

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Reference Intervals of Thyroid Hormones and Correlation of BMI with Thyroid Function in Healthy Zhuang Ethnic Pregnant Women

BioMed Research International ◽

10.1155/2018/2032413 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 1

Author(s):

Yonghong Sheng ◽

Dongping Huang ◽

Shun Liu ◽

Xuefeng Guo ◽

Jiehua Chen ◽

...

Keyword(s):

Thyroid Hormones ◽

Pregnant Women ◽

Thyroid Function ◽

Reference Intervals ◽

Thyroid Stimulating Hormone ◽

Specific Reference ◽

American Thyroid Association ◽

Reference Ranges ◽

Free Triiodothyronine ◽

Cross Sectional

Ethnic differences in the level of thyroid hormones exist among individuals. The American Thyroid Association (ATA) recommends that an institution or region should establish a specific thyroid hormone reference value for each stage of pregnancy. To date, a limited number of studies have reported the level of thyroid hormones in Chinese minorities, and the exact relationship between BMI and thyroid function in pregnant women is ill. This study was performed to establish trimester-specific reference ranges of thyroid hormones in Zhuang ethnic pregnant women and explore the role of body mass index (BMI) on thyroid function. A total of 3324 Zhuang ethnic health pregnant women were recruited in this Zhuang population-based retrospective cross-sectional study. The values of thyroid stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) were determined by automatic chemiluminescence immunoassay analyzer. Multivariate linear regression and binary logistic regression were constructed to evaluate the influence of BMI on the thyroid function. The established reference intervals for the serum thyroid hormones in three trimesters were as follows: TSH, 0.02–3.28, 0.03–3.22, and 0.08-3.71 mIU/L; FT4, 10.57–19.76, 10.05–19.23, and 8.96–17.75 pmol/L; FT3, 3.51–5.64, 3.42–5.42, and 2.93–5.03 pmol/L. These values were markedly lower than those provided by the manufacturers for nonpregnant adults which can potentially result in 6.10% to 19.73% misclassification in Zhuang pregnant women. Moreover, BMI was positively correlated with isolated hypothyroxinemia (OR=1.081, 95% CI=1.007–1.161), while the correlation between the BMI and subclinical hypothyroidism was not statistically significant (OR=0.991, 95% CI=0.917–1.072). This is the first study focusing on the reference ranges of thyroid hormones in Guangxi Zhuang ethnic pregnant women, which will improve the care of them in the diagnosis and treatment. We also found that high BMI was positively associated with the risk of isolated hypothyroxinemia.

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

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2019-0495 ◽

2019 ◽

Vol 57 (12) ◽

pp. 1956-1967 ◽

Cited By ~ 3

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.

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

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/0004563217738801 ◽

2017 ◽

Vol 55 (4) ◽

pp. 446-452 ◽

Cited By ~ 5

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.

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Gestation specific reference intervals for thyroid function tests in pregnancy

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2015-0569 ◽

2016 ◽

Vol 54 (8) ◽

Cited By ~ 6

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

Journal of the Endocrine Society ◽

10.1210/jendso/bvab091 ◽

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.

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The prevalence of thyroid disorders during early pregnancy in China: the benefits of universal screening in the first trimester of pregnancy

Acta Endocrinologica ◽

10.1530/eje-10-0660 ◽

2011 ◽

Vol 164 (2) ◽

pp. 263-268 ◽

Cited By ~ 45

Author(s):

Weiwei Wang ◽

Weiping Teng ◽

Zhongyan Shan ◽

Sen Wang ◽

Jianxin Li ◽

...

Keyword(s):

High Risk ◽

Pregnant Women ◽

Early Pregnancy ◽

Risk Group ◽

First Trimester ◽

Reference Intervals ◽

Case Finding ◽

High Risk Group ◽

Specific Reference ◽

Thyroid Disorders

ContextMaternal thyroid disorders during early pregnancy can influence pregnancy outcome and fetal development. The recent Endocrine Society Clinical Practice Guideline recommends a case-finding approach in which pregnant women who are at high risk for developing thyroid disease are tested.ObjectiveThe purpose of this study was to use the first trimester-specific reference intervals of thyroid-related hormones to explore the prevalence of thyroid dysfunction during early pregnancy and to analyze effectiveness of different screening strategies.DesignA multicenter cohort study.MethodA total of 2899 pregnant women were enrolled in this study during their first trimester of gestation. Levels of TSH, free thyroxine, free triiodothyronine, and thyroid peroxidase antibodies (TPOAb) were measured and thyroid disorders of pregnant women were diagnosed based on the first trimester-specific reference intervals.ResultsThe prevalence of hypothyroidism was significantly higher in the high-risk group than in the non-high-risk group (10.9 vs 7.0%, χ2=7.1, P=0.008). The prevalence of hyperthyroidism was not significantly different between the high-risk group and the non-high-risk group (2.7 vs 1.6%, χ2=2.27, P=0.13). Elevated levels of TPOAb and a personal history of thyroid disease increased the risk of thyroid dysfunction.ConclusionsA case-finding strategy for screening thyroid function in the high-risk group would miss about 81.6% pregnant women with hypothyroidism and 80.4% pregnant women with hyperthyroidism.

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Trimester-Specific Reference Ranges for Thyroid Hormones in Iranian Pregnant Women

Journal of Thyroid Research ◽

10.1155/2013/651517 ◽

2013 ◽

Vol 2013 ◽

pp. 1-6 ◽

Cited By ~ 11

Author(s):

Ladan Mehran ◽

Atieh Amouzegar ◽

Hossein Delshad ◽

Sahar Askari ◽

Mehdi Hedayati ◽

...

Keyword(s):

Thyroid Hormones ◽

Pregnant Women ◽

Thyroid Function ◽

Final Analysis ◽

Reference Intervals ◽

Specific Reference ◽

Reference Ranges ◽

Thyroid Function Tests ◽

Thyroid Disorder ◽

Function Tests

Background. Due to many physiological changes during pregnancy, interpretation of thyroid function tests needs trimester-specific reference intervals for a specific population. There is no normative data documented for thyroid hormones on healthy pregnant women in Iran. The present survey was conducted to determine trimester-specific reference ranges for serum TSH, thyroxine (TT4), and triiodothyronine (TT3).Methods. The serum of 215 cases was analyzed for measurement of thyroid function tests by immunoassay method of which 152 iodine-sufficient pregnant women without thyroid autoantibodies and history of thyroid disorder or goiter were selected for final analysis. Reference intervals were defined as 5th and 95th percentiles.Results. Reference intervals in the first, second, and third trimesters were as follows: TSH (0.2–3.9, 0.5–4.1, and 0.6–4.1 mIU/l), TT4 (8.2–18.5, 10.1–20.6, and 9–19.4 μg/dl), and TT3 (137.8–278.3, 154.8–327.6, and 137–323.6 ng/dl), respectively. No correlation was found between TSH and TT4 or TT3. Significant correlation was found between TT4 and TT3 in all trimesters (r=0.35,P<0.001).Conclusion. The reference intervals of thyroid function tests in pregnant women differ among trimesters. Applying trimester-specific reference ranges of thyroid hormones is warranted in order to avoid misclassification of thyroid dysfunction during pregnancy.

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

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1177/00045632211026955 ◽

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 (2.5â97.5 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 4.40â13.93 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.

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