Verification of selective and individual pulmonary thromboembolism prophylaxes for cesarean delivery.

OBJECTIVE: This study aimed to verify the utility of simple, safe, and effective venous thromboembolism (VTE) prophylaxis and implement it with few adverse events during cesarean delivery. METHODS: This single-center, prospective study involved pregnant women who underwent cesarean deliveries from August 3, 2020 to March 31, 2022. Patients with VTE risk factors were initially administered unfractionated heparin (5,000 international unit [IU] subcutaneously, twice daily), 6 hours after cesarean delivery. Subsequently, they were administered enoxaparin (2,000 IU subcutaneously, twice daily). They were not administered anticoagulants if one or more of the exclusion criteria were met. The primary efficacy outcome was the incidence of symptomatic VTE. The primary safety outcome was the incidence of major bleeding. RESULTS: Out of the 850 women eligible for this study, 551 (64.9%) had one or more VTE risk factors and 299 (35.1%) had no risk factors. Of the 551 women with one or more VTE risk factors, 15 met one or more exclusion criteria for enoxaparin administration. A total of 314 women received only perioperative mechanical prophylaxis, including 15 who met the exclusion criteria for anticoagulants and 299 without VTE risk factors. During implementation of the protocol, no woman developed symptomatic VTE after cesarean delivery. Major bleeding occurred in only one woman who received postoperative anticoagulants. CONCLUSION: This protocol, which clarified the administration of anticoagulants according to VTE risk factors and dose reduction/discontinuation criteria, may be an effective and safe VTE prophylaxis for cesarean deliveries.

Prevalence of common aneuploidy in twin pregnancies.

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04-0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Evaluation of the clinical performance of noninvasive prenatal testing at a Japanese laboratory.

AIM: We aimed to evaluate the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of noninvasive prenatal testing (NIPT) in high-risk pregnant women. METHODS: Pregnant women who underwent GeneTech NIPT, the most commonly used NIPT in Japan, between January 2015 and March 2019, at Japan NIPT Consortium medical sites were recruited for this study. The exclusion criteria were as follows: pregnant women with missing survey items, multiple pregnancy/vanishing twins, chromosomal abnormalities in the fetus other than the NIPT target disease, and nonreportable NIPT results. Sensitivity and specificity were calculated from the obtained data, and maternal age-specific PPV and NPV were estimated. RESULTS: Of the 45 504 cases, 44 263 cases fulfilling the study criteria were included. The mean maternal age and gestational weeks at the time of procedure were 38.5 years and 13.1 weeks, respectively. Sensitivities were 99.78% (95% confidence interval [95% CI]: 98.78-99.96), 99.12% (95% CI: 96.83-99.76), and 100% (95% CI: 88.30-100) for trisomies 21, 18, and 13, respectively. Specificities were more than 99.9% for trisomies 21, 18, and 13, respectively. Maternal age-specific PPVs were more than 93%, 77%, and 43% at the age of 35 years for trisomies 21, 18, and 13, respectively. CONCLUSION: The GeneTech NIPT data showed high sensitivity and specificity in the detection of fetal trisomies 21, 18, and 13 in high-risk pregnant women, and maternal age-specific PPVs were obtained. These results could provide more accurate and improved information regarding NIPT for genetic counseling in Japan.

Congenital contractural arachnodactyly suspected by abnormally long extremities by fetal ultrasound.

Congenital contractural arachnodactyly (CCA) is a rare disease with the clinical features of limited extension of multiple joints, arachnodactyly, camptodactyly, thin and long extremities, and so on. In the point of long extremities, CCA resembles Marfan syndrome (MFS). CCA is easily differentiated from MFS after birth due to the flexion of multiple joints, including elbows, knees, hips and fingers. During the fetal period, observation of arachnodactyly and folded fingers by fetal ultrasound is the means of differential diagnosis between these two diseases. We report on a case of CCA diagnosed with prenatal symptoms of long extremities, and introduced physiotherapy in early childhood for a better physical prognosis.

Retrospective details of false-positive and false-negative results in non-invasive prenatal testing for fetal trisomies 21, 18 and 13.

OBJECTIVE: Maternal characteristics and neonatal outcomes associated with cell-free DNA (cfDNA) results were analysed retrospectively to assess the details of false-positive and false-negative results after initial blood sampling in non-invasive prenatal testing (NIPT). STUDY DESIGN: A multicentre retrospective study was performed for women undergoing NIPT who received discordant cfDNA results between April 2013 and March 2018. The NIPT data obtained using massive parallel sequencing were studied in terms of maternal background, fetal fraction, z-scores, invasive procedure results and neonatal outcomes after birth. RESULTS: Of the 56,545 women who participated in this study, 54 false-positive (0.095 %) and three false-negative (0.006 %) cases were found. Seven of the 54 false-positive cases (13.0 %) had vanishing twin on ultrasonography. Among the 18 false-positive cases of trisomy 18, confined placental mosaicism (CPM) was confirmed in three cases (16.7 %), while CPM was present in one of the three false-negative cases of trisomy 21. CONCLUSION: These data suggest that the incidence of women with false-positive or false-negative results is relatively low, that such false results can often be explained, and that vanishing twin and CPM are potential causes of NIPT failure. Genetic counselling with regard to false results is important for clients prior to undergoing NIPT.

Magnetic resonance relaxometry improves the accuracy of conventional MRI in the diagnosis of endometriosis-associated ovarian cancer: A case report.

Endometriosis is a precancerous condition for endometriosis-associated ovarian cancer (EAOC). In the present study, conventional magnetic resonance imaging (MRI) and MR relaxometry were used to examine a case of clear cell carcinoma that arose in a pre-existing right-sided benign ovarian endometrioma (OE). The 42-year-old nulliparous woman suspected of EOAC, as assessed by conventional MRI, requested fertility-sparing surgery such as laparoscopic endometrioma cystectomy. Furthermore, the MR transverse relaxation rate (R2) was determined using a single-voxel, multi-echo MR sequence using a 3 Tesla-MR system. An R2 value <12.1 s-1 was indicative of malignancy, as described in previous studies. In the present study, MR relaxometry identified an R2 value of 7.98 s-1 in the right cyst, which suggested the malignant transformation of benign OE. Based on these findings, fertility-sparing surgery was contraindicated. In conclusion, MR relaxometry may represent a new clinical approach as an adjunctive modality for the diagnosis of EAOC. When patients exhibiting a pelvic mass suspected of EAOC desire fertility-sparing treatment options, MR relaxometry can facilitate the selection of conservative management.

Placental expression of lysophosphatidic acid receptors in normal pregnancy and preeclampsia.

PROBLEM: Recent advances in lipid research have revealed that impairments in lipid mediator signaling can be involved in the pathoetiology of a variety of diseases. We previously reported aberrant expression of autotaxin, a key enzyme for lysophosphatidic acid (LPA) production, in placentas from women with preeclampsia. The present study aimed to further explore the involvement of LPA signaling in the pathoetiology of preeclampsia. METHOD OF STUDY: Term placentas were obtained from deliveries after uncomplicated pregnancy (n = 18) and those complicated by preeclampsia (n = 24). First-trimester placental tissues were collected after elective terminations of pregnancy (n = 20). Placental expression of the six identified LPARs (LPAR1-6) was analyzed at protein and mRNA levels. RESULTS: In normal pregnancy, the mRNA expression levels of all LPARs except LPAR4 were significantly higher in term. Levels of mRNA encoding LPAR2-5 were significantly increased in preeclampsia placentas compared with those in the normal term placentas. Using Western immunoblotting, only LPAR3 was noted to be increased at the protein level in placentas from preeclamptic pregnancies. This was validated by immunohistochemistry. CONCLUSION: In summary, the placental expression of LPARs, particularly LPAR3, is enhanced in preeclampsia, suggesting that disturbances in placental LPA signaling may be involved in the pathogenesis of preeclampsia.

Placental autotaxin expression is diminished in women with pre-eclampsia.

AIM: Lysophosphatidic acid (LPA) is a member of a new class of lipid mediators and exerts varied physiological and pathological functions. The secreted protein, autotaxin (ATX), is a key enzymatic determinant of local LPA production. The primary aim of this study was to investigate the potential involvement of the placental ATX-LPA system in pre-eclampsia (PE). MATERIAL AND METHODS: We compared human placental ATX mRNA expression in pregnancies complicated by severe PE with that in healthy placentas using real-time polymerase chain reaction. We further assessed whether these expression levels were associated with disease-onset patterns. RESULTS: Placental transcription of ATX increased progressively during normal pregnancy. In the analysis for pre-eclamptic placentas, the placental ATX expression in the early-onset group, but not in late-onset group, was significantly lower compared to normal controls. Multiple regression analysis revealed that occurrence of early-onset PE, but not late-onset PE, was a variable that was significantly associated with the placental ATX expression level. CONCLUSION: These findings support our previous work showing reduced ATX antigen levels in the peripheral blood of pre-eclamptic women. A disturbance in placental ATX production may be linked to poor placental development and systemic maternal symptoms in early-onset PE.

Cervical Expression of Elafin and SLPI in Pregnancy and Their Association With Preterm Labor.

PROBLEM: Elafin and secretory leukocyte peptidase inhibitor (SLPI) are unique among antimicrobial peptides (AMPs). This study aimed to determine the expression levels of these AMPs at the cervix during pregnancy and to investigate their association with preterm labor. METHOD OF STUDY: Cervical epithelial cells were swabbed from normal pregnant women to evaluate the physiological expression of elafin and SLPI. Cross-sectional analysis was conducted to compare cervical expression levels for SLPI and elafin among three women's groups, controls (n = 26), women with threatened preterm labor who delivered at term (t-TPL, n = 23) and TPL who ended in preterm labor (p-TPL, n = 19). RESULTS: Elafin and SLPI proteins were detected in the squamous and glandular cells of the cervix. Cervical SLPI expression levels increased over the course of pregnancy, whereas elafin levels remained unchanged. Cervical mRNA expression levels of elafin and SLPI were significantly higher in p-TPL compared with t-TPL and control groups. CONCLUSION: Constitutive expression of elafin and SLPI in cervical cells during pregnancy suggests their essential roles in local tissue homeostasis and immune defense. The elevations in cervical elafin and SLPI expression in the women with preterm delivery might reflect the local response to the pathogen invasion into the cervix preceding preterm labor.

Emerging roles for lysophospholipid mediators in pregnancy.

Recent progress in lipid research has unveiled new biologic roles for lysophospholipids as mediators of intercellular signaling. Lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) are representative lysophospholipids. Accumulating evidence suggests that, acting as intercellular mediators, these and other lysophospholipids may play important roles in physiological and pathological situations. This review discusses the possible involvement of LPA and S1P in reproductive processes, with a focus on the regulatory mechanisms of pregnancy maintenance. As LPA promotes prostaglandin synthesis, mediators in the LPA pathway may also play a significant role in implantation and parturition. S1P signaling is thought to be essential in vascular formation within the uteroplacental unit and in fetomaternal immunologic interactions. Derangements in either one of these lysophospholipid signaling pathways could result in pregnancy complications that may include implantation failure, preeclampsia, and preterm labor.

Human decidual macrophages suppress IFN-γ production by T cells through costimulatory B7-H1:PD-1 signaling in early pregnancy.

In human pregnancy, CD14⁺ decidual macrophages (DMs) are the dominant professional antigen-presenting cells in the decidua, comprising 20-30% of the local leukocyte population. Although the relevance of DMs to feto-maternal immune tolerance has been described, the molecular mechanisms underlying these functions have not been fully elucidated. B7-H1, a costimulatory ligand in the B7 family, negatively modulates T cell activity by binding to its corresponding receptor, PD-1. The present study aimed to investigate the functional significance of costimulatory interactions between DMs and T cells, with a particular focus on B7-H1:PD-1 signaling. An analysis of the expression profile of B7 ligands on human DMs revealed that B7-H1 was present on DMs isolated from early but not term pregnancies. B7-H1 was not expressed on the peripheral monocytes (PMs) of pregnant women. In response to IFN-γ, B7-H1 expression was induced on PMs and was enhanced on DMs, suggesting that this cytokine might be a key factor in the control of B7-H1 expression in the decidua. The majority of decidual T cells were noted to exhibit robust expression of PD-1, whereas the expression was limited to a small subpopulation of circulating T cells. Functional assays demonstrated that DMs are able to suppress T cell IFN-γ production via B7-H1:PD-1 interactions. This suppressive property was not observed for PMs, which lack B7-H1. B7-H1 on DMs may function as a key regulator of local IFN-γ production and thereby contribute to the development of appropriate maternal immune responses to the fetus in early pregnancy.