Physiological and metabolic adaptations in pregnancy: importance of trimester-specific reference intervals to investigate maternal health and complications

2021 ◽  
pp. 1-17
Author(s):  
Mary Kathryn Bohn ◽  
Khosrow Adeli
Keyword(s):  
Maternal Health ◽  
Reference Intervals ◽  
Specific Reference ◽  
Metabolic Adaptations ◽  
In Pregnancy

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.

scholarly journals Cardiac-specific troponins in uncomplicated pregnancy and pre-eclampsia: A systematic review

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0247946
Author(s):  
Samuel Dockree ◽  
Jennifer Brook ◽  
Brian Shine ◽  
Tim James ◽  
Lauren Green ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Troponin I ◽  
Troponin T ◽  
High Sensitivity ◽  
Reference Intervals ◽  
Careful Consideration ◽  
Blood Levels ◽  
Specific Reference ◽  
Uncomplicated Pregnancy ◽  
In Pregnancy

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.

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.

A Practical Approach for the Verification and Determination of Site- and Trimester-Specific Reference Intervals for Thyroid Function Tests in Pregnancy

Thyroid ◽  
2019 ◽  
Vol 29 (3) ◽  
pp. 412-420 ◽  
Author(s):  
Lois E. Donovan ◽  
Amy Metcalfe ◽  
Alex Chin ◽  
Jennifer M. Yamamoto ◽  
Heidi Virtanen ◽  
...  
Keyword(s):  
Thyroid Function ◽  
Reference Intervals ◽  
Practical Approach ◽  
Specific Reference ◽  
Thyroid Function Tests ◽  
Function Tests ◽  
In Pregnancy

Improving diagnostic accuracy in pregnancy with individualised, gestational age-specific reference intervals

2022 ◽  
Author(s):  
Samuel Dockree ◽  
Brian Shine ◽  
Lawrence Impey ◽  
Lucy Mackillop ◽  
Prof Harpal Randeva ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Gestational Age ◽  
Reference Intervals ◽  
Specific Reference ◽  
In Pregnancy

scholarly journals Narrow intra-individual variation of maternal thyroid function in pregnancy based on a longitudinal study on 132 women

2009 ◽  
Vol 161 (6) ◽  
pp. 903-910 ◽  
Author(s):  
Malene Boas ◽  
Julie Lyng Forman ◽  
Anders Juul ◽  
Ulla Feldt-Rasmussen ◽  
Niels Erik Skakkebæk ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Function ◽  
Individual Variation ◽  
Reference Intervals ◽  
Specific Reference ◽  
Longitudinal Course ◽  
Individual Variations ◽  
Maternal Thyroid ◽  
In Pregnancy

BackgroundAdaptive alterations in maternal physiology cause changes in thyroid hormone levels throughout pregnancy, and precise biochemical evaluation is thus highly dependent on gestation-specific reference intervals and expected intra-individual variation.ObjectiveThe aim of the study was the assessment of the intra-individual variation as well as the longitudinal course of thyroid hormones during normal pregnancy and factors that influence the normal reference range for thyroid function. For this purpose, a longitudinal statistical model was applied.DesignIn a cohort of 132 pregnant women, serial blood samples were obtained and ultrasound scans were performed throughout pregnancy.MethodsSerum levels of TSH, free and total thyroxine (T4), free and total triiodothyronine (T3) as well as autoantibodies against thyroid peroxidase and thyroglobulin were measured in 979 serum samples.ResultsIntra-individual variations of thyroid hormone concentrations were smaller than inter-individual variations (individuality index range: 0.38–0.71). Maternal height was positively associated with free T4 (FT4) (b=0.003; P=0.031) and pre-pregnancy body mass index with T3 and free T3 (b=0.017; <0.001 and b=0.007; P<0.001). Smoking was positively associated with T4 and FT4, but it was modulated by gestational age. Gestation-specific reference intervals for thyroid function variables from autoantibody-negative participants are presented.ConclusionsIn accordance with the data from nonpregnant adults, intra-individual variations of thyroid hormones were smaller than inter-individual variations also during pregnancy. In the evaluation of thyroid function in pregnancy, the individual longitudinal course of thyroid hormones rather than absolute values should be considered. We present a longitudinal model for the prediction of maternal thyroid function tests in pregnant women.

Trimester-specific reference intervals for haemoglobin A1c (HbA1c) in pregnancy

2012 ◽  
Vol 50 (5) ◽  
Author(s):  
Catherine O’Connor ◽  
Paula Mary O’Shea ◽  
Lisa Ann Owens ◽  
Louise Carmody ◽  
Gloria Avalos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Glycaemic Control ◽  
Gestational Diabetes ◽  
Glycated Haemoglobin ◽  
Reference Intervals ◽  
Specific Reference ◽  
Haemoglobin A1c ◽  
Selective Screening ◽  
Diabetes In Pregnancy ◽  
In Pregnancy

AbstractDiabetes in pregnancy imposes additional risks to both mother and infant. These increased risks are considered to be primarily related to glycaemic control which is monitored by means of glycated haemoglobin (HbAThe authors recruited 311 non-diabetic Caucasian pregnant (n=246) and non-pregnant women (n=65). A selective screening based on risk factors for gestational diabetes was employed. All subjects had a random plasma glucose <7.7 mmol/L and normal haemoglobin level. Pregnancy trimester was defined as trimester 1 (T1, n=40) up to 12 weeks +6 days, trimester 2 (T2, n=106) 13–27 weeks +6 days, trimester 3 (T3, n=100) >28 weeks to term.The normal HbAHbA

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
Keyword(s):  
Uric Acid ◽  
Kidney Disease ◽  
Pregnant Women ◽  
Age Groups ◽  
Serum Levels ◽  
Reference Intervals ◽  
Specific Reference ◽  
Serum Urea ◽  
Age Related ◽  
In Pregnancy

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 &lt;.01), and no significant age-related differences in the 3 indicators were observed among the pregnant women (P &gt;.05). However, the levels of these indicators were significantly different among the 3 trimesters (all P &lt;.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.

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