Trimester-specific Reference Intervals Research Articles

Defining gestational thyroid dysfunction through modified non-pregnancy reference intervals: an individual participant meta-analysis.

Establishing local trimester-specific reference intervals for gestational TSH and FT4 is often not feasible, necessitating alternative strategies. We aimed to systematically quantify the diagnostic performance of standardized modifications of center-specific non-pregnancy reference intervals as compared to trimester-specific reference intervals. We included prospective cohorts participating in the Consortium on Thyroid and Pregnancy. After relevant exclusions, reference intervals were calculated per cohort in thyroperoxidase antibody-negative women. Modifications to the non-pregnancy reference intervals included an absolute modification (per 0.1 mU/L TSH or 1 pmol/L FT4), relative modification (in steps of 5%) and fixed limits (upper TSH limit between 3.0 to 4.5 mU/L and lower FT4 limit 5-15 pmol/L). We compared (sub)clinical hypothyroidism prevalence, sensitivity and positive predictive value (PPV) of aforementioned methodologies with population-based trimester-specific reference intervals. The final study population comprised 52,496 participants in 18 cohorts. Optimal modifications of standard reference intervals to diagnose gestational overt hypothyroidism were -5% for the upper limit of TSH and +5% for the lower limit of FT4 (sensitivity 0.70, confidence interval [CI] 0.47-0.86; PPV 0.64, CI 0.54-0.74). For subclinical hypothyroidism, these were -20% for the upper limit of TSH and -15% for the lower limit of FT4 (sensitivity 0.91, CI 0.67-0.98; PPV 0.71, CI 0.58-0.80). Absolute and fixed modifications yielded similar results. Confidence intervals were wide, limiting generalizability. We could not identify modifications of non-pregnancy TSH and FT4 reference intervals that would enable centers to adequately approximate trimester-specific reference intervals. Future efforts should be turned towards studying the meaningfulness of trimester-specific reference intervals and risk-based decision limits.

Defining Trimester-Specific Reference Intervals for Thyroid Hormones: Insights from a Bulgarian Monocenter Study.

Background and Objectives: Pregnancy introduces various interfering factors that, alongside individual variations, impact the assessment of thyroid function tests. This underscores the necessity of defining trimester-specific reference intervals for thyroid-stimulating hormone (TSH) levels. Differences in population characteristics, including ethnicity, socio-economic factors, iodine prophylaxis, and obesity, emphasize the need to establish trimester-specific TSH ranges for women of reproductive age in the respective region or center. The aim of the present study was to establish first- and second-trimester-specific reference intervals for TSH and free thyroxine (FT4) in a relevant pregnant population. Materials and Methods: A retrospective monocenter analysis utilized the electronic database of Ob/Gyn Hospital "Dr. Shterev", Sofia, Bulgaria. The analysis involved data from 497 pregnant and 250 non-pregnant women, all without evidence of thyroid dysfunction or a family history thereof, no indication of taking medication interfering with thyroid function, no evidence of levothyroxine treatment, and no history of sterility treatment. To establish the limits of the TSH reference range, the percentile method was applied using a bootstrapping procedure following the recommendations of the International Federation of Clinical Chemistry (IFCC). Results: Trimester-specific reference intervals for TSH and FT4 in our center were established as follows: first trimester-0.38-2.91 mU/L, FT4-12.18-19.48 pmol/L; second trimester-0.72-4.22 mIU/L and 9.64-17.39 pmol/L, respectively. We also established the normal reference range for the non-pregnant control group, which is similar to that applicable in our laboratory. Conclusions: Our results differ from the fixed limits recommended by the American Thyroid Association, European Thyroid Association, and Endocrine Society Guidelines. Following the relevant established intervals would significantly impact timely diagnosis and therapy requirements for a substantial proportion of pregnant women.

First trimester specific reference interval of TSH, FT3, FT4 in population of Oran (Algeria)

First trimester specific reference interval of TSH, FT3, FT4 in population of Oran (Algeria)

Defining trimester-specific reference intervals for carbohydrate deficient transferrin in pregnant women

ObjectivesExtensive consumption of alcohol during pregnancy can lead to severe complications for the unborn child. Carbohydrate-deficient transferrin (CDT) levels in serum have become a common biomarker for excessive alcohol intake. However, during pregnancy CDT levels can rise to levels above commonly used cut-off values, for reasons unrelated to alcohol intake. The aim of this study is to investigate the changes in CDT values during pregnancy and to determine accurate, trimester dependent reference intervals. Methods439 serum samples of 147 healthy pregnant women were obtained for trimester 1, 2, 3, and post-partum and were analysed by high-performance liquid chromatography (HPLC) and an N-Latex immunonephelometric assay. New trimester-specific reference intervals were established. ResultsThis study demonstrates there is a trimester-dependent increase of %CDT, as up to 39.4% of the population exceeded the previously established upper reference limit of 1.7%. In our study the estimated upper reference limit for %DST/%CDT were 1.55%, 1.96%, 2.05% and 1.35% for trimester 1, 2, 3 and post-partum for the HPLC-method and 2.02%, 2.19%, 2.19% and 1.96% for the N-Latex immunoassay. ConclusionsWe demonstrate that CDT levels rise during pregnancy. The magnitude of the increase is method-dependent and needs to be taken into account. We have established method- and trimester-specific reference intervals to prevent false-positive results in alcohol abuse screening tests during pregnancy.

Establishment of trimester-specific reference intervals of renal function tests and their predictive values in pregnant complications and perinatal outcomes: A population-based cohort study

ObjectivesIn this study, we aimed to establish the trimester-specific RIs of renal function tests (RFTs) in singleton pregnant women and investigate the associations between adverse perinatal outcomes and abnormal renal function laboratory results. MethodsThe results of RFTs and the associated medical records were retrieved from 16489 singleton pregnant women who underwent first- and third-trimester prenatal screening and gave a live birth at out institute between August 2018 and December 2019. The RFTs were performed on the automated immunochemistry platform ARCHITECT ci16200 (Abbott Laboratories Ltd, Abbott Park, Illinois, US) in the clinical laboratory of our institute. The nonparametric 2.5th-97.5th percentile intervals and the indirect Hoffmann methods were used to define the trimester-specific RIs. The associations between abnormal RFTs and adverse pregnancy outcomes was assessed statistically by logistic regression. ResultsThere was no significant difference between the direct observational and the indirect Hoffmann methods in establishing RIs of RFTs. Compared with RFTs in the first trimester, the concentrations of serum BUN and Crea were slightly decreased (p < 0.001), and the serum UA and Cys C levels were significantly elevated in the third trimester (p < 0.001). In the logistic regression analysis, high concentrations of UA, Crea, and Cys C in late pregnancy were associated with an increased risk of postpartum hemorrhage. Meanwhile, early pregnancy UA was associated with a modestly increased risk of GDM, GH, and PE. ConclusionIt is necessary to establish trimester-specific RIs for RFTs, in order to appropriately interpret laboratory results and to identify women with high risks of developing various adverse outcomes.

SAT456 Validation And Optimization Of TSH And FT4 Reference Interval Definitions During Pregnancy

Abstract Disclosure: J. Osinga: None. A. Derakhshan: None. W. Consortium on Thyroid and Pregnancy: None. T. Korevaar: None. Objective: While international guidelines recommend to diagnose gestational thyroid disease according to trimester specific TSH and FT4 reference intervals (RIs), most centers still rely on non-pregnancy RIs in combination with a fixed upper limit for TSH or by a deduction from this upper limit. Both strategies are based on expert opinion and have not been properly validated. We aimed to quantify the diagnostic accuracy of the alternative methods, and to identify the optimal diagnostic strategy to diagnose thyroid disease using a non-pregnancy TSH and FT4 RI. Methods: We performed an individual participant data meta-analysis of prospective birth cohorts. RIs and disease prevalences were calculated according to 1) trimester specific RIs, 2) non-pregnancy RIs, 3) non-pregnancy RIs with a fixed upper limit for TSH of 4.0mU/L and 4) non-pregnancy RIs with a 0.5mU/L subtraction from the TSH upper limit. Sensitivity and false discovery rates (FDR) of the alternative methods were calculated as compared to method 1), which is currently accepted as the best practice. We also varied non-pregnancy RIs with differing subtractions to identify the optimal diagnostic method. Participants with a treatment indication were defined as either overt hypothyroidism, subclinical hypothyroidism with TSH&amp;gt;10 or with concomitant TPOAb positivity. Results: The study population comprised 58,815 participants in 19 prospective cohorts. For first trimester overt hypothyroidism, sensitivity of all alternative methods (non-pregnancy RIs, fixed limit approach, subtraction approach) was similarly poor (0.43, 0.46 and 0.46) with a moderate FDR (0.22, 0.28 and 0.29). For first trimester subclinical hypothyroidism, results were slightly better for all methods, except for the FDR of the subtraction method; sensitivity (0.44, 0.54 and 0.55) and FDR (0.23, 0.23 and 0.35). Using the trimester specific approach, 2.01% of all women had a treatment indication in the first trimester. For this group, both the fixed limit and subtraction approach had a sensitivity of 0.65 and a FDR of 0.11 and 0.17 respectively. Furthermore, we leveraged our dataset to identify how non-pregnancy TSH and FT4 RIs can be used to approach pregnancy-specific RIs. We identified that for a treatment indication, subtraction of 20-25% of the non-pregnancy upper limit of TSH and subtracting 5-10% of the non-pregnancy lower limit of FT4 yielded a higher sensitivity (0.72-0.77) with a comparable FDR (0.20-0.25). Conclusion: Currently recommended alternative methods for defining RIs for TSH and FT4 in pregnancy have poor sensitivity when compared to the currently accepted trimester specific approach, and lead to substantial overdiagnosis. A relative subtraction from the non-pregnancy upper limit of TSH and lower limit of FT4 could considerably improve the diagnostic rates and would be directly available in daily practice. Presentation: Saturday, June 17, 2023

TSH and FT4 Reference Interval Recommendations and Prevalence of Gestational Thyroid Dysfunction: Quantification of Current Diagnostic Approaches.

Guidelines recommend use of population- and trimester-specific thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals (RIs) in pregnancy. Since these are often unavailable, clinicians frequently rely on alternative diagnostic strategies. We sought to quantify the diagnostic consequences of current recommendations. We included cohorts participating in the Consortium on Thyroid and Pregnancy. Different approaches were used to define RIs: a TSH fixed upper limit of 4.0 mU/L (fixed limit approach), a fixed subtraction from the upper limit for TSH of 0.5 mU/L (subtraction approach) and using nonpregnancy RIs. Outcome measures were sensitivity and false discovery rate (FDR) of women for whom levothyroxine treatment was indicated and those for whom treatment would be considered according to international guidelines. The study population comprised 52 496 participants from 18 cohorts. Compared with the use of trimester-specific RIs, alternative approaches had a low sensitivity (0.63-0.82) and high FDR (0.11-0.35) to detect women with a treatment indication or consideration. Sensitivity and FDR to detect a treatment indication in the first trimester were similar between the fixed limit, subtraction, and nonpregnancy approach (0.77-0.11 vs 0.74-0.16 vs 0.60-0.11). The diagnostic performance to detect overt hypothyroidism, isolated hypothyroxinemia, and (sub)clinical hyperthyroidism mainly varied between FT4 RI approaches, while the diagnostic performance to detect subclinical hypothyroidism varied between the applied TSH RI approaches. Alternative approaches to define RIs for TSH and FT4 in pregnancy result in considerable overdiagnosis and underdiagnosis compared with population- and trimester-specific RIs. Additional strategies need to be explored to optimize identification of thyroid dysfunction during pregnancy.

An observational association study between maternal homocysteine and pregnancy complications or perinatal outcomes with established trimester-specific reference intervals in pregnant women.

Elevated homocysteine (Hcy) level during pregnancy is positively associated with various gestational-specific diseases. However, there is no uniform standard for the reference interval (RI) of Hcy in pregnancy. From January 2017 to January 2019, 14,530 singleton pregnant women registered at our institute were included for the establishment of trimester-specific RIs of Hcy with both the nonparametric approach and the indirect Hoffmann method, followed by pregnancy outcome association analysis conducted with logistic regression. The serum Hcy level in the nonpregnant group was significantly higher than that of pregnant women. A relatively decreased Hcy concentration was observed in the second trimester when compared with that of the first or third trimester. The direct RIs of Hcy in the first or third, and second trimesters were 4.6 to 8.0 mmol/L (merged) and 4.0 to 6.4 mmol/L, respectively, which showed no significant difference compared with the RI derived from the indirect Hoffmann method. In the subsequent risk analysis, the first trimester Hcy was found to be negatively associated with GDM development; whereas the third trimester Hcy conferred increased risk of postpartum hemorrhage after delivery. Having established trimester-specific RIs, our study sheds light on the complicated roles of Hcy in pregnancy-related complications.

Trimester-specific reference intervals for hemoglobin A1c in non-diabetic pregnancy in a Chinese population

BackgroundPhysiological glycated hemoglobin (HbA1c) values in each trimester are not well defined. This study aimed to determine trimester-specific reference intervals for HbA1c levels in non-diabetic pregnant women in China.MethodsIn this cross-sectional study, 5,042 Chinese pregnant women from 6 to 41 weeks of gestation were screened. An inclusion of 4,134 non-diabetic women was made to determine the reference intervals, they were divided into three trimesters: trimester 1 (T1), 6 weeks to 13 weeks + 6 days, trimester 2 (T2), 14 weeks to 27 weeks + 6 days, and trimester 3 (T3), 28 weeks to 41 weeks + 6 days. A total of 4,134 women (T1 n = 760, T2 n = 1,953, and T3 n = 1,421) provided blood samples which were analyzed for HbA1c concentrations. HbA1c was measured using high-performance liquid chromatography. The median and percentile (2.5th to 97.5th) for the HbA1c reference intervals were calculated for each trimester.ResultsIn total, 8,732 HbA1c measurements were taken. Reference intervals for HbA1c expressed as median and percentile (2.5th to 97.5th) for each trimester were: T1: 4.7 (4.0–5.5%), T2: 4.5 (3.9–5.3%), and T3: 4.8 (4.1–5.7%) respectively. The HbA1c levels were significantly lower in the second trimester compared to those in the first trimester (p < 0.0001), and higher in the third trimester compared to the second trimester (p < 0.0001).ConclusionsThe reference intervals for HbA1c levels were 3.9–5.7% with upper limits of 5.5% in the first trimester, 5.3% in the second trimester, and 5.7% in the third trimester. These findings highlight the importance of considering trimester-specific reference intervals for HbA1c in non-diabetic pregnant women to promote maternal and fetal health.

Trimester-specific reference intervals of serum homocysteine levels for pregnant women: a longitudinal study in China

Objective To investigate the physiological changes of serum homocysteine (Hcy) levels and to establish trimester-specific reference intervals of serum Hcy levels for Chinese pregnant women. Method According to the guideline of the Clinical and Laboratory Standards Institute (CLSI) C28-A3 document, 476 healthy women were recruited in West China Second University Hospital, Sichuan University from January 2021 to October 2021. Among them, 120 were non-pregnant, 118 were in the first trimester, 120 were in the second and 118 were in the third trimester of gestation. The enzymatic cycling method was performed to detect serum Hcy levels. Non-parametric percentiles (2.5th percentile and 97.5th percentile) were calculated to establish the reference intervals for non-pregnant women and pregnant women in different trimester of gestation. Results There was a significant statistical difference for serum Hcy levels between non-pregnant women and pregnant women (p < 0.05), and serum Hcy levels in the first, second, and third trimesters of gestation were statistically different (p < 0.05). The trimester-specific reference intervals of serum Hcy levels were 4.35 ∼ 10.16 μmol/L, 3.38 ∼ 8.60 μmol/L, and 3.75 ∼ 11.17 μmol/L for pregnant women in the first, second, and third trimester of gestation, respectively. Conclusions Compared to non-pregnant women, serum Hcy levels physiologically decreased after pregnancy, and the physiological changes in serum Hcy levels during pregnancy were also found. Establishing trimester-specific reference intervals of serum Hcy levels for pregnant women was valuable for clinical practice.

Trimester-specific reference intervals of hemostasis biomarkers for healthy pregnancy

Physiological changes in hemostasis during pregnancy have been reported by several authors. This study aimed at establishing reference intervals for the hemostasis biomarkers thrombin-antithrombin complex (TAT), α2-plasmininhibitor-plasmin complex (PIC), thrombomodulin (TM) and tissue plasminogen activator-inhibitor complex (tPAI-C), in healthy pregnancies. After excluding outliers, a total of 496 healthy pregnant women (128 first-trimester, 142 second-trimester, 107 third-trimester and 119 pre-labor) and 103 healthy nonpregnant women were enrolled from Shenzhen Bao’an Women’s and Children’s Hospital. Hemostasis biomarkers, TAT, PIC, TM and tPAI-C, were measured by using a quantitative chemiluminescence enzyme immunoassay performed on HISCL automated analysers. The median and reference intervals (the 2.5th and 97.5th percentiles) were calculated to establish trimester-specific reference intervals for healthy pregnant women. The reference intervals for TAT, PIC, TM and tPAI-C in the first trimester were 0.7–7.6 1 µg/L, 0.2–0.9 mg/L, 2.8–11.0 TU/ml, and 1.2–6.5 1 µg/L, respectively. The reference intervals in the second trimester were 1.7–12.0 1 µg/L, 0.2–1.0 mg/L, 3.7–11.6 TU/ml, and 2.8–8.8 1 µg/L, respectively. The reference intervals in the third trimester were 2.7–16.1 1 µg/L, 0.1–1.4 mg/L, 2.9–12.9 TU/ml, and 1.9–8.0 1 µg/L, respectively. At pre–labor, the reference intervals were 4.8–32.9 1 µg/L, 0.2–1.9 mg/L, 4.2–12.6 TU/ml, and 2.8–15.4 1 µg/L, respectively. Gestational reference intervals for TAT, PIC, TM and tPAI-C in healthy pregnancies are provided, but only for TAT with increasing concentrations throughout pregnancy, the reference intervals for non-pregnant were not applicable.

Trimester-specific reference intervals and profile of coagulation parameters for Chinese pregnant women with diverse demographics and obstetric history: a cross-sectional study

BackgroundOwing to the changes in childbirth policy in China, this work aimed to update the trimester-specific reference intervals (RIs) for Chinese pregnant women with diverse demographics and obstetric history. This study also investigated how advanced maternal age (AMA) (> 35 years old), gravity, and parity influence gestational coagulation parameters.MethodsIn this prospective cross-sectional study, five coagulation parameters were measured using assays provided by Roche diagnostics on Cobas t 711: prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fib), and D-dimer, and the trimester-specific 2.5th -97.5th and 95th (D-dimer only) percentiles RIs were established accordingly. Linear regressions were undertaken to analyze the association with demographic characteristics and obstetric history for each parameter.Results893 eligible pregnant women in different trimesters and at AMA/non-AMA and 275 non-pregnant healthy women were enrolled. For the first, second, and third trimester, respectively, RIs were as follows: APTT (s): 24.8–35.7, 24.6–34.1, and 23.5–34.7; TT (s): 14.4–17.3, 14.1–16.7, and 14.2–17.5; PT (s): 8.30–10.20, 8.00-9.77, and 7.92–9.57; PT-INR: 0.86–1.06, 0.83–1.02, and 0.82–0.98; Fib (g/L): 2.76–4.97, 3.14–5.31, and 3.44–5.93; D-dimer (µg/ml): 0-0.969, 0-2.14, and 0-3.28. No statistically significant differences were observed in TT, D-dimer, and APTT between the AMA and non-AMA women, while PT and PT-INR were shorter and Fib was higher in the AMA group. The association of gravidity and parity with each coagulation parameter is statistically significant (p < 0.05). PT and PT-INR were shortened and D-dimer decreased as gravidity increased. Longer PT and PT-INR, shorter APPT, higher D-Dimer, and lower Fib were associated with increasing parity.ConclusionsThis work updated the gestational coagulation profiles of Chinese pregnant women and established trimester-specific RIs accordingly. Establishing specific RIs based on AMA, parity, and gravidity might not be necessary.

Elevated levels of renal function tests conferred increased risks of developing various pregnancy complications and adverse perinatal outcomes: insights from a population-based cohort study.

Physiological changes during pregnancy can affect the results of renal function tests (RFTs). In this population-based cohort study, we aimed to establish trimester-specific reference intervals (RIs) of RFTs in singleton and twin pregnancies and systematically investigate the relationship between RFTs and adverse pregnancy outcomes. The laboratory results of the first- and third-trimester RFTs, including blood urea nitrogen (BUN), serum uric acid (UA), creatinine (Crea) and cystatin C (Cys C), and the relevant medical records, were retrieved from 29,328 singleton and 840 twin pregnant women who underwent antenatal examinations from November 20, 2017 to January 31, 2021. The trimester-specific RIs of RFTs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between RTFs and pregnancy complications as well as perinatal outcomes were assessed by logistic regression analysis. Maternal RFTs showed no significant difference between the direct RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. In addition, elevated levels of RFTs were associated with increased risks of developing various pregnancy complications and adverse perinatal outcomes. Notably, elevated third-trimester RFTs posed strong risks of preterm birth (PTB) and fetal growth restriction (FGR). We established the trimester-specific RIs of RFTs in both singleton and twin pregnancies. Our risk analysis findings underscored the importance of RFTs in identifying women at high risks of developing adverse complications or outcomes during pregnancy.

Development and validation of risk prediction models for large for gestational age infants using logistic regression and two machine learning algorithms.

Large for gestational age (LGA) is one of the adverse outcomes during pregnancy that endangers the life and health of mothers and offspring. We aimed to establish prediction models for LGA at late pregnancy. Data were obtained from an established Chinese pregnant women cohort of 1285 pregnant women. LGA was diagnosed as >90th percentile of birth weight distribution of Chinese corresponding to gestational age of the same-sex newborns. Women with gestational diabetes mellitus (GDM) were classified into three subtypes according to the indexes of insulin sensitivity and insulin secretion. Models were established by logistic regression and decision tree/random forest algorithms, and validated by the data. A total of 139 newborns were diagnosed as LGA after birth. The area under the curve (AUC) for the training set is 0.760 (95% confidence interval [CI] 0.706-0.815), and 0.748 (95% CI 0.659-0.837) for the internal validation set of the logistic regression model, which consisted of eight commonly used clinical indicators (including lipid profile) and GDM subtypes. For the prediction models established by the two machine learning algorithms, which included all the variables, the training set and the internal validation set had AUCs of 0.813 (95% CI 0.786-0.839) and 0.779 (95% CI 0.735-0.824) for the decision tree model, and 0.854 (95% CI 0.831-0.877) and 0.808 (95% CI 0.766-0.850) for the random forest model. We established and validated three LGA risk prediction models to screen out the pregnant women with high risk of LGA at the early stage of the third trimester, which showed good prediction power and could guide early prevention strategies.

Establishing Trimester-Specific Haemoglobin A1c Reference Intervals in Pregnant Women: A retrospective study of healthy South Asian women with normal pregnancy outcomes.

This study aimed to define trimester-specific haemoglobin A1c (HbA1c) reference intervals in healthy, pregnant South Asian women. This retrospective study was conducted at St. Stephen's Hospital, Delhi, India, between January 2011 and December 2016. Healthy pregnant women were compared to a control group of healthy non-pregnant women. Pregnant participants had term deliveries of babies with appropriate gestational weights. The HbA1c levels were calculated in terms of non-parametric 2.5 and 97.5 percentiles for women in first (T1), second (T2) and third (T3) trimester groups. Statistical tests were used to obtain the normal HbA1c reference values and were considered significant when P <0.05. This study included a total of 1,357 healthy pregnant women and a control group of 67 healthy, non-pregnant women. Pregnant women had a median HbA1c of 4.8% (4-5.5%) or 32 mmol/mol (20-39 mmol/mol); non-pregnant women had a median HbA1c of 5.1% (4-5.7%) or 29 mmol/mol (20-37 mmol/mol; P <0.001). The HbA1c levels for the T1, T2 and T3 groups were 4.9% (4.1-5.5%) or 30 mmol/mol (21-37 mmol/mol), 4.8% (4.5-5.3%) or 29 mmol/mol (20-34 mmol/mol) and 4.8% (3.9-5.6%) or 29 mmol/mol (19-38 mmol/mol), respectively. The HbA1c values were significant when comparing T1 versus T2 (P <0.001), T1 versus T3 (P = 0.002) and T1 versus the non-pregnant group (P = 0.001). However, T2 versus T3 was not significant (P = 0.111). Compared to non-pregnant women, HbA1c levels were lower in pregnant women, despite women in the T2 and T3 groups having a higher body mass index than the women in the T1 and non-pregnant groups. Further research is recommended to understand the factors responsible and validate these findings.

Thyroid hormone status during pregnancy in Bangladesh

ABSTRACT Background: Pregnancy is a physiological condition where early detection of any pathological change of thyroid hormone is very important to prevent complications. Population-specific thyroid hormone reference intervals are a key to this. Since Bangladesh is yet to develop such reference intervals, the aim of this study was to establish trimester-specific reference intervals addressing the physiological changes of thyroid hormone during pregnancy for Bangladeshi women. Materials and Methods: One thousand nine hundred and thirty-seven women with singleton pregnancy consuming iodinated salt were selected for this cross-sectional study. Participants having a history of thyroid disorder (TD), any illness influencing thyroid function, presence of goiter, recent history of consumption of thyroid status-altering medications, family history of TDs, and presence of thyroid antibodies were excluded from the study. 1038 pregnant women with thyroid-stimulating hormone (TSH) level within normal (nonpregnant) laboratory reference value (0.35–5.5 μIU/mL) were considered eligible for the study. Results: The mean age of the eligible cases was 28.06 ± 4.633 years ranging from 18 years to 42 years. The mean gestational ages of the study population while checking thyroid function were 8.83 ± 2.344 weeks, 19.99 ± 4.824 weeks, and 31.77 ± 2.123 weeks during 1st, 2nd, and 3rd trimesters, respectively. TSH level raised significantly from 1st trimester to 2nd trimester (1.85 ± 1.00 vs. 2.03 ± 1.02; P = 0.018) but the decline in 3rd trimester comparing to 2nd trimester (2.03 ± 1.02 vs. 1.90 ± 0.90; P = 0.071) was not statistically significant. The 2.5th–97.5th percentiles of TSH level of the study population were 0.440–4.050 μIU/mL, 0.531–4.570 μIU/mL, and 0.622–3.917 μIU/mL in 1st, 2nd, and 3rd trimesters, respectively. Conclusion: Reliance on nonpregnant reference intervals or any generalized gestational reference interval can hinder the desired progression of pregnancy influencing diagnosis and management for TDs in case of certain populations. Establishment of individual reference intervals for thyroid hormone in pregnancy bears great clinical importance for every population.

Explore the impact of abnormal coagulation test results on pregnancy complications and perinatal outcomes by establishing the trimester-specific reference intervals of singleton and twin pregnancies

BackgroundDuring pregnancy, complex physiological changes take place in the hemostatic system, resulting in a hypercoagulable state. With the established trimester-specific reference intervals (RIs) of the coagulation tests, we investigated the associations between disturbance of hemostasis and adverse pregnant outcomes in a population-based cohort study. MethodsThe first- and third-trimester coagulation tests results were retrieved from 29,328 singleton and 840 twin pregnant women for regular antenatal check-ups from November 30th, 2017 to January 31st, 2021. The trimester-specific RIs for fibrinogen (FIB), prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), d-dimer (DD) were estimated using both the direct observational and the indirect Hoffmann methods. The associations between the coagulation tests and the risks of developing pregnancy complications as well as adverse perinatal outcomes were assessed using the logistic regression analysis. ResultsIncreased FIB, DD and decreased PT, APTT and TT were observed as the gestational age increases in the singleton pregnancy. An enhanced procoagulant state, marked by significant elevation of FIB, DD and reduction of PT, APTT and TT, was observed in the twin pregnancy. The subjects with anormal PT, APTT, TT, DD, tend to have increased risks of developing peri- and postpartum complications such as preterm birth, fetal growth restriction. ConclusionsThe incidence of adverse perinatal outcomes was remarkably associated with the maternal increased levels of FIB, PT, TT, APTT and DD in the third trimester, which may be applied in early identification of women at high risk of adverse outcomes due to coagulopathy.

Thyroid-Stimulating Hormone Levels within the Trimester-Specific Reference Intervals Are Correlated with Non-High-Density Lipoprotein Cholesterol and Remnant Cholesterol Concentrations in Pregnant Women.

Thyroid-stimulating hormone (TSH) levels are associated with serum lipid concentrations in the general nonpregnant population. Here, we aimed to establish trimester-specific reference intervals and to explore the associations of their variations within the specific reference intervals during pregnancy. Trimester-specific reference intervals were established according to the Clinical and Laboratory Standard Institute EP28-A3c guidelines using a direct sampling method based on a large prospective cohort. After making one-to-one matches, correlation analyses between TSH and lipid index levels, especially within the reference intervals, were conducted. A total of 1648 pregnant women for TSH and 2045 subjects for lipids were recruited to establish the trimester-specific reference intervals. The upper reference limit (90% confidence interval) of TSH for pregnant women in the first trimester is 3.95 (3.66-4.29) mIU/L, which is very close to the default value (4.0 mIU/L) recommended by the American Thyroid Association in 2017. Apart from triglyceride and high-density lipoprotein cholesterol, TSH levels were positively associated with the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C), and remnant cholesterol (RC) either in the entire range or within the specific reference intervals. Of note, the positive correlations between TSH and non-HDL-C and RC were, albeit similarly weak (r < 0.25), relatively more robust (P < .001). In this study, we showed positive correlations between TSH and lipid components within trimester-specific reference intervals, highlighting the need for the integrated management of pregnant women over age 35 and with nonoptimal lipid status in China.

Low haptoglobin in pregnancy: physiological or intravascular hemolysis?

Abstract A woman in her second trimester of pregnancy (24 weeks of gestation), diagnosed with B-cell acute lymphoblastic leukemia, received induction chemotherapy. On day six of treatment, she required transfusion with two red cell (RBC) units for anemia. Less than 12 hours later, laboratory results included elevated total bilirubin, 4.3 mg/dL [reference interval &amp;lt;=1.2 mg/dL], direct bilirubin, 0.3 mg/dL [reference interval &amp;lt;=0.3 mg/dL], haptoglobin below detection limit, &amp;lt;10 mg/dL [reference interval: 30 - 200 mg/dL], and normal lactate dehydrogenase (LD), 186 U/L [reference interval: 122 - 241 U/L]. These tests were ordered without any clinical suspicion for intravascular hemolysis, and upon receiving the results, the primary team consulted transfusion medicine due to concern for an acute hemolytic transfusion reaction (AHTR). After finishing the corresponding workup, the patient did not meet the Center of Disease Control (CDC) criteria for AHTR. The patient was discharged and on follow-up visits her haptoglobin increased to 15 mg/dL (25 weeks 3 days of gestation). Later, during her third trimester (27 weeks 3 day of gestation), haptoglobin increased to 142 mg/dL; LD always remained normal. Hemolysis is not associated with normal LD. Instead, some literature suggest that pregnant patients may have lower haptoglobin levels than reported in the non-pregnant population, with a nadir occurring in the second trimester. It is possible that low haptoglobin in this population may be due to the combination of hemodilution and a high estrogen state. But no literature is available that provide trimester-specific reference intervals for haptoglobin, which may lead to misinterpretation. Inspired by this case, we developed a quality improvement project to determine trimester-specific reference intervals for haptoglobin in pregnancy. Haptoglobin was tested on remnant serum samples (BD Vacutainer SST) collected from routine outpatient pregnancy patients (n=401; at least 80 samples per trimester) using Roche/Hitachi cobas c systems. Derived nonparametric reference intervals were 22-188 mg/dL for first trimester, 29-177 mg/dL for second trimester, 53-185 mg/dL for third trimester, and 30-185 mg/dL for the entire sample population. While overall reference intervals were similar, consistent with previous reports, we noticed a shift in haptoglobin distribution to the low end in the second trimester [29 (CI95% 7-35) mg/dL; median 98 mg/dL] in comparison with first trimester [22 (CI95% 15-47) mg/dL; median 113 mg/dL p = 0.34] and third trimester [29 (CI95% 7-35); median 112 mg/dL p=0.34].In the case described, the first haptoglobin below limit of detection could have been due to the combination of pregnancy (second trimester), recent red cell transfusion of RBC units (28 days old) and hyperhydration with crystalloids as part of the chemotherapy plan. This case also serves as a reminder that laboratory tests should be ordered mindfully, to aid in confirming or ruling out clinically suspected syndromes/diseases that are unlikely.

The Significance of Trimester-Specific Thyroid Hormones Reference Intervals in Iraqi Pregnant Women

In Iraq, there is no obvious considerable data regarding trimester-specific reference intervals of thyroid hormones despite documented multiple physiological hormonal changes during pregnancy. Thus, this study aimed to determine trimester-specific reference intervals for serum TSH, FT3, and FT4 and assess the incidence of thyroid function test misinterpretation and misdiagnosis among pregnant women using non-pregnant reference intervals. A thyroid function test was performed for 774 enrolled pregnant women. Reference intervals of TSH, FT3, and FT4 were ascertained in each pregnancy trimester. It was then compared to the adult non-pregnant values, and the incidence of misinterpretation was later calculated. TSH and FT4 reference interval values were lower than non-pregnant reference interval values. The application of non-pregnant women references values in pregnant women caused a serious misinterpretation and misdiagnosis in 66 (8.5%) pregnant women regarding TSH, and 34 (4.4%) pregnant women regarding FT4, while no misdiagnosis was noticed regarding FT3. The trimester-specific reference interval values of TSH, FT3, and FT4 in Iraqi pregnant women showed an obvious variation from non-pregnant reference intervals and the urgent advice to use the trimester-specific reference intervals to avoid misclassification of thyroid dysfunction during pregnancy.