Previous adverse pregnancy outcomes (APO) in women with hereditary thrombophilia have emerged as new indications for prophylactic use of low-molecular-weight heparin (LMWH) during pregnancy. Recent meta-analysis conducted to establish if LMWH may prevent recurrent placenta-mediated pregnancy complications point to important therapeutic effect but these findings are absolutely not universal. Furthermore, previous studies regarding LMWH prophylaxis for APO in women with inherited thrombophilia were performed in high risk patients with previous adverse health outcomes in medical, family and/or obstetric history. Therefore, the aim of this study was to investigate the effects of LMWH prophylaxis on pregnancy outcomes in women with inherited thrombophilias regardless of the presence of previous adverse health outcomes in medical, family, and obstetric history.
Prospective analytical cohort study included all referred women with inherited thrombophilia between 11 and 15 weeks of gestation and followed-up to delivery. Patients were allocated in group with LWMH prophylaxis (study group) and control group without LWMH prophylaxis. The groups were compared for laboratory parameters and Doppler flows of umbilical artery at 28
th
to 30th, 32nd to 34th and 36th to 38th gestational weeks (gw), and for obstetric and perinatal outcomes.
The study group included 221 women and control group included 137 women. Mean resistance index of the umbilical artery Ri in 28 to 30, 32 to 34, and 36 to 38 gw were significantly higher in the control group compared to study group (0.71 ± 0.02 vs 0.69 ± 0.02; 0.67 ± 0.03 vs 0.64 ± 0.02; and 0.67 ± 0.05 vs 0.54 ± 0.08, respectively). Intrauterine fetal death (IUFD) and miscarriages were statistically significantly more frequent in control group compared to the patients in study (
P
< .001). The frequencies of fetal growth restriction (FGR) and APO were significantly higher in the control group compared to the study group (
P
= .008 and
P
< .001, respectively). In a multivariate regression model with APO as a dependent variable, only Ri was detected as a significant protective factor for APO, after adjusting for age and LMWH prophylaxis (
P
< .001).
We have demonstrated better perinatal outcomes in women with LMWH prophylaxis for APO compared to untreated women.
Mucins are multifunctional highly glycosylated proteins expressed by the female reproductive tract. Differential expression of MUC1 and MUC15 has been shown in trophoblast. This study was undertaken to establish the distribution of mucin(s) in cytotrophoblast cell cultures using anti-bovine submaxillary mucin (BSM) and to investigate the possibility of MUC1/mucin(s) being a binding partner of trophoblast galectin-1. MUC1 is demonstrated here using immunocytochemistry on isolated cytotrophoblast and the HTR-8/SVneo extravillous trophoblast cell line but detection of additional trophoblast mucins cannot be excluded. Western blot analysis showed similar bands ranging from 30 to >200 kDa with anti-BSM and the well-known mucin antibodies HMFG1 and B72.3. Immunocytochemistry and cell-based ELISA data were found to support that all of the antibodies used are reactive with BSM, suggesting the presence of shared epitopes between BSM and trophoblast mucin(s). Binding of galectin-1 to trophoblast MUC1/mucin(s) was analyzed using a solid-phase assay and co-immunoprecipitation. Recombinant galectin-1 binding to isolated trophoblast mucin in solid-phase assay was sensitive to lactose, a carbohydrate inhibitor of galectin binding. In whole HTR-8/SVneo lysates, ~200 kDa mucin was detected in galectin-1 immunoprecipitates, while endogenous galectin-1 was present in BSM-immunoprecipitates. Furthermore, double fluorescence immunocytochemistry showed overlap of galectin-1 and trophoblast mucins at the plasma membrane of HTR-8/SVneo cells. These results suggest that trophoblast mucin(s) could act as binding partners of galectin-1, in a carbohydrate-dependent manner.
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