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.

Objectives: In 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. Methods: The 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. Results: There 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. Conclusion: It 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.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Having established trimester-specific RIs, our study sheds light on the complicated roles of Hcy in pregnancy-related complications.

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.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

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.

BACKGROUND: During 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. METHODS: The 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. RESULTS: Increased 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. CONCLUSIONS: The 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.

Establishment of trimester-specific reference intervals of serum lipids and the associations with pregnancy complications and adverse perinatal outcomes: a population-based prospective study.

BACKGROUND: Disturbances in maternal lipid metabolism may increase the risk of developing pregnancy complications and adverse perinatal outcomes. However, there is no consensus as to what constitutes normal serum lipid ranges during pregnancy. Our study was aimed to establish trimester-specific serum lipid reference intervals (RIs) and investigate the associations between maternal dyslipidaemia and adverse outcomes in a population-based study. METHODS: The first- and third-trimester lipid profiles were derived from 16,489 singlet pregnant women for regular antenatal check-ups between 2017 and 2019. The serum samples were assayed for total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-C), and low-density lipoprotein-cholesterol (LDL-C) in the institutional clinical laboratory. The trimester-specific lipid RIs were estimated with both of the direct observational and the indirect Hoffmann methods. The associations between maternal lipid profiling and pregnancy complications and perinatal outcomes were assessed statistically. RESULTS: Serum levels of TC, TG, LDL-C and HDL-C were all increased significantly in the third trimester of pregnancy. There was no significant difference between the observed RIs established with healthy pregnant women and the calculated RIs derived from the Hoffmann method. A trend towards increased risks of gestational complications and adverse perinatal outcomes was observed in the subjects with elevated levels of TC, TG, and LDL-C or decreased level of HDL-C. CONCLUSIONS: In pregnancy, increased serum levels of TC, TG and LDL-C, and a decreased level of HDL-C posed higher risks of developing pregnancy complications and adverse perinatal outcomes.Key messagesIt is necessary to establish trimester-specific reference intervals for serum lipids including TC, TG, LDL-C and HDL-C that were found significantly increased as the gestational age went up. More importantly, around the upper reference limits of TC, TG and LDL-C (or the lower reference limit of HDL-C), the higher the serum lipid levels were (or the lower the HDL-C level was), the higher risks of developing pregnancy complications and adverse perinatal outcomes were observed.

Thromboelastography (TEG) in normal pregnancy and its diagnostic efficacy in patients with gestational hypertension, gestational diabetes mellitus, or preeclampsia.

BACKGROUND: Thromboelastography (TEG) provides global assessment of hemostatic function and has been recommended to monitor potential coagulopathies during pregnancy in which hypercoagulable state is favored. In present study, we established the reference intervals (RIs) of the TEG parameters (R, K, MA, and α-angle) with Chinese pregnant women of third trimester. In addition, we examined the diagnostic efficacies of the TEG parameters in the patients diagnosed of gestational hypertension (GH), gestational diabetes mellitus (GDM), or preeclampsia (PE). METHODS: With specified including and excluding criteria, non-pregnant controls, healthy pregnant women, and pregnant women with GH, GDM, or PE had their venous blood drawn at Beijing Obstetrics and Gynecology Hospital, followed by TEG tests performed in the clinical laboratory. RESULTS: The RIs determined with the healthy pregnant women (in third trimester) for R, K, MA, and α-angle were 4.0-7.7, 1.2-3.2, 51.9-70.1, and 41.4-74.4, respectively. When compared with the healthy pregnancy group, the K value was significantly decreased in GH patients but increased in PE patients; MA was significantly lower in the PE group. In the receiver operating characteristic curve (ROC) analyses, K value was able to efficiently distinguish normal pregnancy from the GH patients, with an AUC of 0.86 which is far better than those of R (AUC = 0.57) and MA (AUC = 0.56). For the PE patients, the AUC of MA (0.69) was significantly greater than that of R (0.50). CONCLUSIONS: Thromboelastography may provide more accurate experimental basis for monitoring coagulation functions especially in pregnant women with complications of GH and PE.

Glycated albumin in pregnancy: reference intervals establishment and its predictive value in adverse pregnancy outcomes.

BACKGROUND: Many efforts have been focused on the alternative glycemic marker glycated albumin (GlyA) and its application in pregnancy during which profound physiological changes take place. Our objective was to determine the reference intervals (RIs) of GlyA in healthy Chinese pregnant women and to assess the predictive value of serum GlyA in adverse pregnancy outcomes. METHODS: Totally 421 healthy subjects including 137 in the first trimester, 152 in the second trimester, and 132 in the third trimester were enrolled from March to July 2019, for the purpose of establishing the trimester-specific RIs of GlyA. In addition, 67 pregnant women diagnosed with GDM were enrolled at 24-28 weeks of gestation. The diagnostic value of GlyA for GDM patients was evaluated and compared with that of fasting plasma glucose (FPG) at 24-28 weeks of gestation. The association between GlyA in the late pregnancy and the adverse pregnancy outcomes was analyzed with the data collected from January to June 2018 at our hospital. RESULTS: The estimated RIs of GlyA in present study were 11.26-15.10%, 10.04-13.50%, and 9.76-13.09% in the first, second, and third trimesters respectively. The areas under receiver operating characteristic (ROC) curves were 0.503 for GlyA and 0.705 for FPG. More importantly, the GlyA level in the third trimester was not more elevated in the patients with adverse pregnancy outcomes including large for gestational age (LGA), preterm delivery, hypertension and preeclampsia (PE). The exception was made with the GDM patients who suffered from postpartum hemorrhage and had significantly higher GlyA levels than the control group. CONCLUSIONS: Our results showed that the GlyA was continuously decreased as the gestational age went up. The GlyA testing has limited value in diagnosing GDM and predicting adverse pregnancy outcomes.

Reference intervals of trimester-specific thyroid stimulating hormone and free thyroxine in Chinese women established by experimental and statistical methods.

BACKGROUND: As a result of physiological and metabolic changes during pregnancy, thyroid hormones can be affected significantly throughout entire three trimesters. According to the guidelines published by American Thyroid Association in 2017, it is strongly recommended to establish population-based trimester-specific and assay method-specific reference intervals (RIs) using local population. METHODS: A total of 1209 pregnant women without personal or family history of thyroid disease were recruited from July 2015 to April 2017 at Beijing Obstetrics and Gynecology Hospital. Those initially selected patients were further tested for TSH, FT4 and thyroid peroxidase antibody (aTPO), performed on the chemiluminescent platform Siemens ADVIA Centaur® XP. Only patients tested negative for aTPO were included in reference interval establishment. RIs for both TSH and FT4 were determined as 2.5th percentile to 97.5th percentile on the data distribution. RESULTS: The TSH and FT4 trimester-specific RIs were as follows: 0.59-3.54 mIU/L, 11.8-18.4 pmol/L (n = 188, 1st trimester); 0.80-4.46 mIU/L, 11.6-17.4 pmol/L (n = 133, 2nd trimester); 0.72-4.19 mIU/L, 9.7-15.1 pmol/L (n = 157, 3rd trimester). The RIs of TSH and FT4 determined by Hoffmann method for first trimester outpatient pregnant women were 0.33-3.96 mIU/L (n = 9924) and 11.7-17.5 pmol/L (n = 10039), respectively. CONCLUSION: Trimester-specific thyroid function tests RIs are distinct from those provided by assay manufacturers. The RIs determined by direct sampling and Hoffmann indirect calculation showed no statistical difference.