Trimester-Specific Reference Intervals of Serum Urea, Creatinine, and Uric Acid Among Healthy Pregnant Women in Zhengzhou, China

2020 ◽  
Author(s):  
Yuhua Gao ◽  
Jia Jia ◽  
Xianan Liu ◽  
Shuren Guo ◽  
Liang Ming

Abstract Objective To verify the differences in serum levels of urea, creatinine, and uric acid (UA) between pregnant and nonpregnant women and establish specific reference intervals of serum urea, creatinine, and UA for pregnant women, and thus help for the detection of kidney disease in pregnancy. Methods Based on the selection criteria, 1312 apparently healthy pregnant women and 1301 nonpregnant women were enrolled in this study. The levels of serum urea, creatinine, and UA were compared between the pregnant and nonpregnant women. The differences in the 3 indicators among different age groups and trimesters in pregnant women were studied. Finally, reference intervals were established by nonparametric methods according to the recommendation of Clinical and Laboratory Standards Institute guideline C28-A3. Results Compared with nonpregnant women, pregnant women had a significantly lower level of serum urea, creatinine, and UA (all P <.01), and no significant age-related differences in the 3 indicators were observed among the pregnant women (P >.05). However, the levels of these indicators were significantly different among the 3 trimesters (all P <.01 or P =.01). Accordingly, trimester-specific reference intervals of serum urea (1.6–4.4 mmol/L; 1.6–4.2 mmol/L; 1.6–4.4 mmol/L), creatinine (36–68 μmol/L; 34–66 μmol/L; 36–68 μmol/L), and UA (122–297 μmol/L; 129–327 μmol/L; 147–376 μmol/L) for trimesters 1, 2, and 3, respectively, were established. Conclusion These newly established reference intervals will be valuable for the detection and monitoring of kidney disease in pregnancy.

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247946
Author(s):  
Samuel Dockree ◽  
Jennifer Brook ◽  
Brian Shine ◽  
Tim James ◽  
Lauren Green ◽  
...  

Background The risk of myocardial infarction (MI) increases during pregnancy, particularly in women with pre-eclampsia. MI is diagnosed by measuring high blood levels of cardiac-specific troponin (cTn), although this may be elevated in women with pre-eclampsia without MI, which increases diagnostic uncertainty. It is unclear how much cTn is elevated in uncomplicated and complicated pregnancy, which may affect whether the existing reference intervals can be used in pregnant women. Previous reviews have not investigated high-sensitivity troponin in pregnancy, compared to older, less sensitive methods. Methods Electronic searches using the terms “troponin I” or “troponin T”, and “pregnancy”, “pregnancy complications” or “obstetrics”. cTn levels were extracted from studies of women with uncomplicated pregnancies or pre-eclampsia. Results The search identified ten studies with 1581 women. Eight studies used contemporary methods that may be too insensitive to use reliably in this clinical setting. Two studies used high-sensitivity assays, with one reporting an elevation in troponin I (TnI) in pre-eclampsia compared to uncomplicated pregnancy, and the other only examining women with pre-eclampsia. Seven studies compared cTn between women with pre-eclampsia or uncomplicated pregnancy using any assay. Seven studies showed elevated TnI in pre-eclampsia compared to uncomplicated pregnancy or non-pregnant women. One study measured troponin T (TnT) in pregnancy but did not examine pre-eclampsia. Conclusion TnI appears to be elevated in pre-eclampsia, irrespective of methodology, which may reflect the role of cardiac stress in this condition. TnI may be similar in healthy pregnant and non-pregnant women, but we found no literature reporting pregnancy-specific reference intervals using high-sensitivity tests. This limits broader application of cTn in pregnancy. There is a need to define reference intervals for cTn in pregnant women, which should involve serial sampling throughout pregnancy, with careful consideration for gestational age and body mass index, which cause dynamic changes in normal maternal physiology.


Author(s):  
Samuel Dockree ◽  
Jennifer Brook ◽  
Brian Shine ◽  
Tim James ◽  
Manu Vatish

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.


2021 ◽  
Vol 9 ◽  
Author(s):  
Chengjun Dai ◽  
Chaoban Wang ◽  
Fangqin Xia ◽  
Zishuo Liu ◽  
Yiqi Mo ◽  
...  

Context: Hyperuricemia is defined when the plasma uric acid concentration is above 416 μmol/L (7 mg/dl) in male adults, or 357 μmol/L (6 mg/dl) in female adults. However, there are no explicit criteria yet for children.Objective: It is necessary to set up reference intervals for the uric acid level in different age groups among children.Materials and Methods: A total of 5,439 individuals (3,258 males, 2,181 females) were included in the final statistical analysis. Reference values of all age groups were determined by statistical descriptions. Multiple linear regression analysis was applied to determine the relationship between uric acid level, BMI, and age.Results: The level of uric acid increased with age. Gender differences in uric acid level occurred after the onset of puberty. Additionally, linear regression revealed a positive correlation between the uric acid level and BMI.Discussion and Conclusion: The reference range of the uric acid level in children is inconsistent with the previous viewpoint. Body mass index plays an important role in uric acid metabolism.


Author(s):  
O E Okosieme ◽  
Medha Agrawal ◽  
Danyal Usman ◽  
Carol Evans

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.


2021 ◽  
Author(s):  
K Aaron Geno ◽  
Matthew S Reed ◽  
Mark A Cervinski ◽  
Robert D Nerenz

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.


2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yonghong Sheng ◽  
Dongping Huang ◽  
Shun Liu ◽  
Xuefeng Guo ◽  
Jiehua Chen ◽  
...  

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.


2020 ◽  
Vol 182 (5) ◽  
pp. 459-471
Author(s):  
Marco Mezzullo ◽  
Guido Di Dalmazi ◽  
Alessia Fazzini ◽  
Margherita Baccini ◽  
Andrea Repaci ◽  
...  

Objective To evaluate the independent impact of age, obesity and metabolic risk factors on 13 circulating steroid levels; to generate reference intervals for adult men. Design Cross-sectional study. Methods Three hundred and fifteen adults, drug-free and apparently healthy men underwent clinical and biochemical evaluation. Thirteen steroids were measured by LC-MS/MS and compared among men with increasing BMI. Moreover, the independent impact of age, BMI and metabolic parameters on steroid levels was estimated. Upper and lower reference limits were generated in steroid-specific reference sub-cohorts and compared with dysmetabolic sub-cohorts. Results We observed lower steroid precursors and testosterone and increase in estrone levels in men with higher BMI ranges. By multivariate analysis, 17-hydroxyprogesterone and dihydrotestosterone decreased with BMI, while cortisol decreased with waist circumference. Estrone increased with BMI and systolic blood pressure. Testosterone decreased with worsening insulin resistance. 17-hydroxypregnenolone and corticosterone decreased with increasing total/HDL-cholesterol ratio. Age-related reference intervals were estimated for 17-hydroxypregnenolone, DHEA, 17-hydroxyprogesterone, corticosterone, 11-deoxycortisol, cortisol and androstenedione, while age-independent reference intervals were estimated for progesterone, 11-deoxycorticosterone, testosterone, dihydrotestosterone, estrone and estradiol. Testosterone lower limit was 2.29 nmol/L lower (P = 0.007) in insulin resistant vs insulin sensitive men. Furthermore, the upper limits for dihydrotestosterone (−0.34 nmol/L, P = 0.045), cortisol (−87 nmol/L, P = 0.045–0.002) and corticosterone (−10.1 nmol/L, P = 0.048–0.016) were lower in overweight/obese, in abdominal obese and in dyslipidaemic subjects compared to reference sub-cohorts, respectively. Conclusions Obesity and mild unmedicated metabolic risk factors alter the circulating steroid profile and bias the estimation of reference limits for testosterone, dihydrotestosterone, cortisol and corticosterone. Applying age-dependent reference intervals is mandatory for steroid precursors and corticosteroids.


2019 ◽  
Vol 119 (06) ◽  
pp. 894-898
Author(s):  
Gao-Ming Zhang ◽  
Wei Zhang ◽  
Guo-Ming Zhang

Background Parturient women are healthy individuals who require special consideration. Parturient women are considered to be in a hyper-coagulable state. For example, the fibrinogen (FIB) levels are often higher than the upper limit of normal reference intervals (RIs) in parturient women than in non-parturient healthy individuals (2–4 g/L). Objective The aim of this study is to establish the RIs of pro-thrombin time (PT), activated partial thromboplastin time (aPTT), FIB levels and thrombin time (TT) for parturient women. Materials and Methods Blood levels of PT, aPTT, FIB and TT were assayed on an ACL TOP 700 automatic coagulation analyser using plasma samples from 10,472 parturient women. Outlier results were excluded by using Tukey's test. The RIs were calculated by the Clinical and Laboratory Standards Institute C28-A3 guideline. Results The RIs of PT, aPTT, FIB and TT were 8.7 to 12.1 seconds (8.7–12.2 seconds for 16–20 years old, 8.7–12.1 second for 21–25 years old, 8.6–12.0 second for 26–30 years old, 8.7–12.0 second for 31–35 years old, 8.7–12.6 second for 36–40 years old and 8.8–12.2 second for 41 years old), 22.9 to 42.3 seconds, 1.98 to 5.82 g/L and 9.9 to 16.7 seconds, respectively. PT levels were found to be positively associated with aging. Conclusion The above-established age-specific RIs, defined by using a large dataset, may assist clinicians in making accurate medical decisions. This was the first study in which the RIs of PT, aPTT, FIB and TT were established for parturient women in different age groups.


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

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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