Pregnancy outcomes in women with mechanical prosthetic heart valves: a prospective descriptive population based study using the United Kingdom Obstetric Surveillance System (UKOSS) data collection system.

OBJECTIVE: To describe the incidence of mechanical prosthetic heart valves (MPHV) in pregnancy in the UK; rates of maternal and fetal complications in this group of women, and whether these vary with the anticoagulation used during pregnancy. DESIGN: Prospective descriptive population-based study. SETTING: All consultant-led maternity units in the UK. POPULATION: All women with an MPHV who were pregnant between 1 February 2013 and 31 January 2015. METHODS: Collection and analysis of anonymous data relating to pregnancy management and outcome, using the UKOSS notification and data collection system. MAIN OUTCOME MEASURES: Maternal death, serious maternal morbidity, poor fetal outcome. RESULTS: Data were obtained for 58 women giving an estimated incidence of 3.7 (95% CI 2.7-4.7) per 100 000 maternities. There were five maternal deaths (9%); a further 24 (41%) suffered serious maternal morbidity. There was a poor fetal outcome from 26 (47%) pregnancies. Only 16 (28%) women had a good maternal and good fetal outcome. Low-molecular-weight heparin (LMWH) was used throughout pregnancy by 71% of women. Of these, 83% required rapid dose escalation in the first trimester. Monitoring regimens lacked consistency. CONCLUSIONS: This study has estimated the incidence of MPHV in pregnant women in the UK. It includes the largest cohort managed with LMWH throughout pregnancy reported to date. It demonstrates a high rate of maternal death, and serious maternal and fetal morbidity. Women with MPHVs, and their clinicians need to appreciate the significant maternal and fetal risks involved in pregnancy. Care should be concentrated in specialist centres. TWEETABLE ABSTRACT: High rates of poor maternal and fetal outcomes in pregnant women with mechanical prosthetic heart valves.

Syncytin 1 in the human placenta.

This study characterises HERV-W (syncytin 1) expression in normal and pathologic placenta and in BeWo cells. HERV-W mRNA levels were higher in the first trimester than at term, and similar patterns were observed with another retrovirally-derived mRNA species, ERV-3. N-glycosylated syncytin 1 precursor (73 kDa) is cleaved to surface-associated (SU) and transmembrane (TM) subunits. Both were evident in villous trophoblast, where perinuclear and punctate cytoplasmic deposits were observed, and linear TM subunit immunoreactivity was seen at the syncytial microvillous membrane. Punctate immunoreactivity was seen in BeWo cells with antibodies to SU and TM, and the two were co-localised. SU immunoreactivity was observed in association with fetal endothelium, and this effect was increased in tissue from pre-eclamptic placentas, which also showed a higher level of total SU protein. Absence of the TM subunit from endothelium suggests it is not a biosynthetic source. We suggest that SU is released from trophoblast into fetal circulation where it may bind vascular endothelium.

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal-fetal interface: potential roles in early placental development.

Angiotensin II (Ang II) is locally generated in the placenta and regulates syncytial transport, vascular contractility and trophoblast invasion. It acts through two receptor subtypes, AGTR1 and AGTR2 (AT1 and AT2), which typically mediate antagonising actions. The objectives of this study are to characterise the cellular distribution of AGTR1 and AGTR2 at the maternal-fetal interface and explore the effects on cytotrophoblast turnover. Low levels of AGTR2 mRNA were detected in first trimester placental homogenates using real-time PCR. Immunohistochemistry using polyclonal antibodies against AGTR1 and AGTR2 detected the receptors in first trimester placenta, decidua basalis and villous tip outgrowths in culture. Serial staining with cytokeratin-7 was used to identify extravillous trophoblasts (EVTs). AGTR1 was found in the syncytiotrophoblast microvillous membrane, in a subpopulation of villous cytotrophoblasts, and in Hofbauer cells. AGTR1 was strongly upregulated in cytotrophoblasts in cell columns and villous tip outgrowths, but was absent in interstitial and endovascular EVTs within the decidua. AGTR2 immunostaining was present in Hofbauer cells and villous cytotrophoblasts, but was absent from syncytiotrophoblast. Faint staining was detected in cell column cytotrophoblasts and villous outgrowths, but not in EVTs within the decidua. Both receptors were detected in placental homogenates by western blotting. Ang II significantly increased proliferation of cytotrophoblasts in both villous explants and villous tip outgrowths, but did not affect apoptosis. Blockade of AGTR1 and AGTR2 together abrogated this effect. This study shows specific expression patterns for AGTR1 and AGTR2 in distinct trophoblast populations at the maternal-fetal interface and suggests that Ang II plays a role in placental development and generation of EVTs.

Transforming growth factor beta1 regulates angiotensin II type I receptor gene expression in the extravillous trophoblast cell line SGHPL-4.

The angiotensin II type 1 (AT1) receptor, transforming growth factor beta1 (TGFbeta1) and Oncostatin M (OSM) control key pathways that may be important during placentation. Although interactions between them exist in other tissues, trophoblast cells have not been investigated. Extravillous trophoblast cells, SGHPL-4, were stimulated with 10 ng/ml TGFbeta1 +/- 100 ng/ml OSM for 24 h. Real-time PCR showed that AT1 expression increased 2.76-fold [95% confidence interval (CI) = 1-6.74, P = 0.05] in response to TGFbeta1 and 4.21-fold (95% CI = 1.33-11.76, P = 0.03) with TGFbeta1 + OSM. Luciferase reporter gene constructs containing three haplotypes of the 59 flanking region of the AT1 receptor gene were transfected into SGHPL-4 and HepG2 cells and stimulated with 0.1, 1 and 10 ng/ml TGFbeta1 and 50 ng/ml OSM. Responses were dose and cell dependent. Luciferase activity increased in HepG2 cells in response to TGFbeta1 alone or together with OSM (P < 0.001); transcriptional activation differed between AT1 receptor gene haplotypes. In SGHPL-4 cells, luciferase activity was reduced on exposure to low concentrations of TGFbeta1 or high concentrations of TGFbeta1 combined with OSM (P = 0.003); the response was unaffected by haplotype. Interaction between AT1 and TGFbeta1 is a novel observation in trophoblast and suggests new avenues for the study of placentation.

Intrauterine haematomas in a recurrent miscarriage population.

BACKGROUND: This study examines the effect of intrauterine haematomas (IUH) discovered during early pregnancy ultrasound scanning in patients with recurrent miscarriage. Previous studies of IUHs have reported conflicting findings, and none studied women with recurrent miscarriage. METHODS: A total of 341 women with a viable pregnancy was included. Women with an IUH (n = 41) were compared with those without (n = 300). RESULTS: An IUH was identified by ultrasound in 12% (41/341) women. There were no differences in the number of live births between the two groups (25/41, 61% in the IUH group compared with 169/300, 56% without an IUH) or the number of miscarriages (6/41, 15% with an IUH compared with 72/300, 24% without an IUH). Anti-phospholipid antibodies were more common in the IUH group (21/31, 68% compared with 103/244, 42% P < 0.01). More women with haematomas experienced vaginal bleeding (16/31, 52% compared with 47/244, 19%, P < 0.01). These associations did not affect pregnancy outcome. Also, no increase in the rate of pregnancy complications was observed in the IUH group. CONCLUSIONS: The presence of an IUH in this potentially high risk patient group does not have a deleterious effect on pregnancy outcome.

Long-term implications of caesarean section.

Previous reports have linked caesarean section with subsequent reduced fertility, increased rates of miscarriage/ectopic, time delay to next baby and lower fetal weight. However, most reports studied women delivering before 1980. The aim of this study was to assess whether these findings still apply. Five hundred and seventy-six primiparous women delivered by caesarean section during 1992-93 and 576 controls were identified and followed for five years. No difference was observed for the time (months) to next pregnancy/delivery, proportion suffering miscarriage or ectopic or the number of subsequent children (P > 0.05, Mann-Whitney U/chi-squared). Subgroup analysis by indication for caesarean section yielded similar results. Subsequent babies in the caesarean section group were statistically smaller and delivered earlier (median 3.4 kg/39 weeks, P <0.01, Mann-Whitney U) compared with the control group (median 3.5 kg/40 weeks). These differences are probably due to an increased rate of elective caesarean section in the caesarean section group. This study has largely refuted the findings of previous publications. Women delivered by caesarean section in the 1990s can be reassured that future fertility and miscarriage/ectopic risk will not be affected.