Pregnancy-specific reference intervals for BNP and NT-pro BNP – changes in natriuretic peptides related to 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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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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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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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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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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THE DIFFERENCE IN ADDITION OF BACK MASSAGE COMBINATION IN PREGNANCY EXERCISE IN IMPROVING QUALITY OF SLEEP IN THIRD TRIMESTER PREGNANT WOMEN

Majalah Ilmiah Fisioterapi Indonesia ◽

10.24843/mifi.2018.v06.i02.p03 ◽

2018 ◽

Vol 6 (2) ◽

pp. 16

Author(s):

Mezzi Wulandari Arenza ◽

Ni Wayan Tianing ◽

I Putu Adiartha Griadhi

Keyword(s):

Sleep Quality ◽

Pregnant Women ◽

Control Group ◽

Quality Of Sleep ◽

Third Trimester ◽

The Third ◽

The Difference ◽

In Pregnancy ◽

Back Massage

ABSTRACTSleep disturbance in the third trimester pregnant women is caused by discomfort, an increasingly largeabdominal condition, back pain, frequent urination, fetal movement, heartburn, cramps in the legs, tiredness, difficultygetting started, and physiological changes. Sleep disorders result in decreased quality of sleep. Pregnant women whohave poor sleep quality are at risk of longer labor, cesarean delivery, premature birth, and even infant mortality. The aimof this research is to know the difference of pregnant exercise combination and back massage in improving the sleepquality of third trimester pregnant women. This research use experiment method with quasi experiment approach andresearch design is pre and post test with control design. Sample are 18 people, divided into 2 groups, 9 people intreatment groups given pregnancy exercise and back massage and 9 people in control group is given only pregnantexercise. Intervention is given 8 times. Pittsburgh Sleep Quality Index (PSQI) questionnaire used for measured of sleepquality. The result of different test of unpaired group, in the treatment group got difference of average 4,556 and controlgroup got difference mean 2,333 with p=0,004 (p<0,05). These results showed that there was a significant differencebetween the treatment group and the control group in improving the sleep quality of the third trimester pregnant women.In conclusion, there are differences in the addition of back massage combination in pregnancy exercise intervention inimproving sleep quality of third trimester pregnant women.Keyword : Pregnancy Exercise, Back Massage, Sleep Quality, Third Trimester.

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

Nutrients ◽

10.3390/nu13114037 ◽

2021 ◽

Vol 13 (11) ◽

pp. 4037

Author(s):

Carla Martín-Grau ◽

Ramón Deulofeu ◽

Nuria Serrat Orus ◽

Victoria Arija ◽

Keyword(s):

Fatty Acids ◽

Pregnant Women ◽

Large Population ◽

First Trimester ◽

Reference Intervals ◽

Gas Chromatography Mass Spectrometry ◽

Specific Reference ◽

Reference Ranges ◽

Maternal Factors ◽

Developed Country

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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Comparison of Salivary Alpha-Amylase, Sialic Acid, and pH in Pregnant and Nonpregnant Subjects

European Journal of General Dentistry ◽

10.1055/s-0041-1732771 ◽

2021 ◽

Author(s):

Masoomeh Shirzaiy ◽

Zohreh Dalirsani

Keyword(s):

Sialic Acid ◽

Pregnant Women ◽

First Trimester ◽

Control Group ◽

Case Group ◽

Third Trimester ◽

The Third ◽

Significant Difference ◽

Salivary Ph ◽

The Mean

Abstract Objectives During pregnancy, systemic physiological alterations lead to some changes in the oral cavity, which could prepare the mouth environment for oral and dental problems. This study was aimed to investigate salivary α-amylase, sialic acid levels, and pH levels in pregnant and nonpregnant females. Materials and Methods In this analytical, case–control study, unstimulated saliva samples were collected with spiting method from 35 pregnant women (case group) and 35 nonpregnant women (control group) and transferred to the laboratory to assess salivary α-amylase, sialic acid, and pH levels. Data were analyzed by SPSS (version: 19) software through statistical methods of independent t-test and analysis of variance. Results The mean sialic acid levels were 2.285 ± 1.230 mg/dL in pregnant and 2.744 ± 1.326 in nonpregnant women without any significant difference (p = 0.138). The mean salivary α-amylase concentrations were 2.461 ± 1.869 U/L and 2.439 ± 2.058 U/L, respectively, in pregnant and nonpregnant women, with no significant difference (p = 0.963).The mean salivary pH in nonpregnant women was significantly more than that in pregnant women (7.845 ± 0.430 and 6.868 ± 0.413, respectively) (p < 0.001). Also, the mean salivary pH levels in pregnant women were 7.474 ± 0.420 in the first trimester, 6.868 ± 0.413 in the second trimester, and 6.568 ± 0.387 in the third trimester, which were significantly different (p < 0.001). Conclusion Salivary sialic acid and α-amylase levels among pregnant women were no different from those of other subjects. During pregnancy, the salivary pH significantly reduced, and the mean salivary pH during pregnancy had a decreasing trend from the first trimester to the third trimester.

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Association of Iodine-Related Knowledge, Attitudes, and Behaviours with Urinary Iodine Excretion in Pregnant Women with Mild Iodine Deficiency

10.21203/rs.3.rs-44718/v1 ◽

2020 ◽

Author(s):

Zhengyuan Wang ◽

Yiwen Wu ◽

Zehuan Shi ◽

Jun Song ◽

Guoquan Wang ◽

...

Keyword(s):

Pregnant Women ◽

Iodine Deficiency ◽

Urinary Iodine ◽

Significant Risk ◽

First Trimester ◽

Iodized Salt ◽

Urinary Iodine Excretion ◽

Urinary Iodine Concentration ◽

Third Trimester ◽

The Third

Abstract Background: China’s universal salt-iodization program has all but eliminated iodine deficiency disorders. Concern has shifted to mild iodine deficiency. Our study examined factors with the potential to predict mild iodine deficiency in pregnant women. Methods: A total of 2 400 pregnant women were enrolled using a multistage, stratified, random-sampling method. Data were collected through face-to-face interviews, a standardized questionnaire, an iodine-related knowledge questionnaire, urine samples, and household cooking salt samples. Results: The median urinary iodine concentration (MUIC) was 148.0 μg/L for all participants, and 155.0 μg/L, 151.0 μg/L, and 139.6 μg/L in the first, second, and third trimesters, respectively. The third trimester’s MUIC was significantly lower than that of the first trimester, and the usage rates of iodized salt and qualified-iodized salt were 71.5% and 59.4%, respectively. Iodine-related knowledge was significantly different between the high and low UIC groups. Participants’ MUIC increased significantly with increases in iodine-related knowledge. The third trimester was a significant risk factor for high UIC, whereas abundant iodine-related knowledge, study the dietary knowledge urgently, and consumption of iodine-rich food within 48 hours of a urine iodine test were significant protective factors for high UIC (P<0.05). Conclusions: Iodine levels are adequate among pregnant women in Shanghai during the first and second trimesters, but insufficient in the third trimester. The use of iodized cooking salt does not determine the iodine status of pregnant women. Abundant iodine-related knowledge is important for pregnant women in the third trimester to maintain adequate urinary iodine.

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First Trimester Ferritin Is Superior over Soluble Transferrin Receptor and Hepcidin in Predicting Anemia in the Third Trimester: Result from a Cohort Study in Indonesia

Anemia ◽

10.1155/2020/8880045 ◽

2020 ◽

Vol 2020 ◽

pp. 1-6

Author(s):

Raden Tina Dewi Judistiani ◽

Tita Husnitawati Madjid ◽

Budi Handono ◽

Hadyana Sukandar ◽

Setyorini Irianti ◽

...

Keyword(s):

Cohort Study ◽

Transferrin Receptor ◽

Serum Ferritin Level ◽

Ferritin Level ◽

First Trimester ◽

Diagnostic Study ◽

Soluble Transferrin Receptor ◽

Third Trimester ◽

The Third ◽

In Pregnancy

Introduction. Anemia in the third trimester has been identified as a risk factor for maternal and fetal morbidity that might lead to mortality. Due to its high cost, finding the best marker to predict anemia became more important to allow early prevention. Only one of ferritin, hepcidin, or soluble transferrin receptors can be picked for the prediction of anemia in the third trimester especially in low-resource setting. Objective. This study aimed at defining the best marker among ferritin, hepcidin, or soluble transferrin receptor (sTfR) in the first trimester for prediction of anemia in the third trimester. Materials, Methods, and Setting. This diagnostic study was nested on the cohort study of vitamin D and its impact during pregnancy in Indonesia. Singleton pregnant mothers with normal fetus were recruited in the first trimester from four cities in West Java, Indonesia. The 304 pregnant women were screened for hepcidin, ferritin, and sTfR level in the sera. All biomarkers were measured by ELISA. Complete blood count (CBC) was done by impedance method measurement (SysmexR). Only subjects with complete data were included in analysis for diagnostic study to compare the three markers by finding the best receiver operating curve (RoC), likelihood ratio (LR), and risk estimate (RR). Result. One-hundred and eighty-one pregnant women were eligible for analysis. The result of this study showed that the serum ferritin level in the first trimester was the best marker to predict anemia in the third trimester of pregnancy. Hepcidin and sTfR performed poorly. A new cutoff point of ferritin level ≤27.23 ng/ml yielded the best ROC with 67% area under curve (95% CI 60%–75%, p<0.0001, Youden index J 0.28), specificity 86.29% (95% CI 79.0%–91.8%), LR (+) 3.07 (95% CI 1.8–5.3), and RR 2.48 (95% CI 1.67–3.68). These last figures were better than the previously used cutoff point of ferritin level below 30 ng/ml. Conclusion. This study provided evidence that the serum ferritin level ≤27.23 ng/ml in the first trimester was the best marker to predict anemia in the third trimester. It was valuably useful for secondary screening of anemia in pregnancy, targeting subjects who may need rigorous approach for iron deficiency treatment in the prevention of anemia in pregnancy.

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