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.

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.

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.

Detection of non-criteria autoantibodies in women without apparent causes for pregnancy loss.

BACKGROUND: Some of the non-criteria autoantibodies, especially non-conventional antiphospholipid (aPL) antibodies, were present with high prevalence in sporadic miscarriages and recurrent pregnant loss. However, whether these autoantibodies are associated with miscarriage patients without apparent causes remain unclear. METHODS: The subjects were recruited from the female patients visiting the Infertility Center at the Beijing Obstetrics and Gynecology Hospital from January 2017 to March 2018. The women who experienced one sporadic miscarriage (n = 89) or recurrent pregnancy loss (n = 125) were enrolled. The control participants (n = 59) were those women with normal pregnancy history and with no miscarriage or thrombosis experience. The collected serum specimens from above patients and controls were subjected to the 13 non-criteria autoantibody examinations, targeting non-conventional phospholipids, thyroid, sperm, endometrial, and anti-nuclear antigens. RESULTS: When compared with the controls, the following non-criteria antibodies stood out in present study with significantly increased frequency and were listed in the order of decreasing positive rates: aPE IgM (40.0%), ANA (15.2%), aEM IgG (13.6%), aPE IgG (12.8%), and aPT IgM (10.4%). Except for ANA, the presence of aPE IgM, aEM IgG, aPE IgG, and aPT IgM was not associated with positivity of LA tests. In receiver operating characteristic analyses, the combined aPE IgG and aEM IgG biomarker panel had the best discriminating power between miscarriage patients and healthy controls. CONCLUSION: Our findings suggested that the non-criteria could be included as part of the pregnancy loss evaluation when apparent causes are absent, and the conventional aPLs tests failed to provide interpretations.