Michelle R. Wise

Successful but limited use of external cephalic version in Auckland.

Background: External cephalic version (ECV) can effectively reduce the chance of non‐cephalic presentation at birth and reduce caesarean section rate for breech presentation at term. It is recommended in New Zealand to offer ECV to all eligible women with breech presentation at term.

Increased levels of HMGB1 in trophoblastic debris may contribute to preeclampsia

Preeclampsia is triggered by an as yet unknown toxin from the placenta. Antiphospholipid antibodies (aPL), a strong risk factor for preeclampsia, have been shown to induce the production of toxic trophoblastic debris from the placenta. High mobility group box 1 (HMGB1) is a proinflammatory danger signal, and the expression of it has been reported to be increased in preeclampsia. This study examined whether aPL or preeclamptic sera increase the expression of HMGB1 in the syncytiotrophoblast or trophoblastic debris. Trophoblastic debris from normal placental explants that had been cultured with aPL or preeclamptic sera was exposed to endothelial cells. Endothelial cell activation was quantified by cell-surface ICAM-1 expression and U937 monocyte adhesion. The expression of HMGB1 in placental explants and trophoblastic debris that had been treated with aPL or preeclamptic sera was measured by immunohistochemistry and western blotting. The expression of the receptor for advanced glycation end products (RAGE) in endothelial cells was quantified by western blotting. Compared with controls, the expression of HMGB1 in the cytoplasm of the syncytiotrophoblast and trophoblastic debris was increased by treating placental explants with aPL or preeclamptic sera. The increased levels of HMGB1 contributed to endothelial cell activation, mediated in part by the RAGE. Preeclamptic sera and aPL both induced an increase in the cytoplasmic levels of the danger signal HMGB1 in trophoblastic debris. This increased HMGB1 in trophoblastic debris may be one of the toxic factors released from the placenta in preeclampsia.

Maternal health in pregnancy and associations with adverse birth outcomes: Evidence from Growing Up in New Zealand

To examine prospectively multiple indicators of pregnancy health and associations with adverse birth outcomes within a large, diverse sample of contemporary women.

In vivo targets of human placental micro-vesicles vary with exposure time and pregnancy

Throughout human gestation, the placenta extrudes vast quantities of extracellular vesicles (EVs) of different sizes into the maternal circulation. Although multinucleated macro-vesicles are known to become trapped in the maternal lungs and do not enter the peripheral circulation, the maternal organs and cells that smaller placental micro-vesicles interact with in vivo remain unknown. This study aimed to characterise the interaction between placental micro-vesicles and endothelial cells in vitro and to elucidate which organs placental micro-vesicles localise to in vivo Placental macro- and micro-vesicles were isolated from cultured human first trimester placental explants by sequential centrifugation and exposed to human microvascular endothelial cells for up to 72 h. In vivo, placental macro- and micro-vesicles were administered to both non-pregnant and pregnant CD1 mice, and after two or 30 min or 24 h, organs were imaged on an IVIS Kinetic Imager. Placental EVs rapidly interacted with endothelial cells via phagocytic and clathrin-mediated endocytic processes in vitro, with over 60% of maximal interaction being achieved by 30 min of exposure. In vivo, placental macro-vesicles were localised exclusively to the lungs regardless of time of exposure, whereas micro-vesicles were localised to the lungs, liver and kidneys, with different distribution patterns depending on the length of exposure and whether the mouse was pregnant or not. The fact that placental EVs can rapidly interact with endothelial cells and localise to different organs in vivo supports that different size fractions of placental EVs are likely to have different downstream effects on foeto-maternal communication.

Placenta praevia after prior caesarean section: an exploratory case-control study.

To identify additional risk factors for placenta praevia in women with prior caesarean section.

Ethnic disparities in repeat caesarean rates at Auckland Hospital

New Zealand guidelines recommend that information regarding childbirth choices be given to women with previous caesarean, so they can make informed decisions about their care. We hypothesised that rates of trial of labour (TOL) and vaginal birth after caesarean (VBAC) would vary by womens ethnicity.

Treating normal early gestation placentae with preeclamptic sera produces extracellular micro and nano vesicles that activate endothelial cells.

OBJECTIVES Preeclampsia is characterised by systemic endothelial cell dysfunction thought to be triggered by toxic/dangerous factors from the placenta, including placental extracellular vesicles (EVs). Why placental EVs become toxic is unknown. We previously reported that preeclamptic sera produced toxic/dangerous placental macrovesicles but whether small EVs are also toxic/dangerous in preeclampsia is unknown. STUDY DESIGN First trimester placental explants were treated with 10% preeclamptic or control sera (n=10) for 24h. Micro- and nano-vesicles were harvested by sequential centrifugation. Micro- or nano-vesicles were also exposed to monolayers of endothelial cells in the presence or absence of nifedipine (50μg/ml) or labetalol (0.5μg/ml) which are well-known anti-hypertensives in clinical practices. MAIN OUTCOMES MEASURES The number and size of micro- and nano-vesicles were counted. Endothelial cell-surface intercellular adhesion molecule 1 (ICAM-1) and high mobility group box 1 (HMGB1) levels in micro- or nano-vesicles were measured by immunoassays. RESULTS Neither the amount nor size of both micro- and nano-vesicles was different after treating placental explants with preeclamptic or control sera. The levels of HMGB1 were significantly increased in both micro- and nano-vesicles from preeclamptic sera treated placental explants (p<0.03). Exposing endothelial cells to micro- or nano-vesicles from preeclamptic sera-treated placental explants induced endothelial activation, but it was reversed by co-incubation with nifedipine (p=0.004) or labetalol (p=0.002). CONCLUSION Our data demonstrate that preeclamptic sera produce toxic/dangerous micro- and nano-placental EVs which activated endothelial cells. This effect was reversed by antihypertensives. The increased levels of HMGB1 in EVs may contribute to endothelial cell activation.

Late stillbirth post mortem examination in New Zealand: Maternal decision‐making

For parents who experience stillbirth, knowing the cause of their babys death is important. A post mortem examination is the gold standard investigation, but little is known about what may influence parents’ decisions to accept or decline.

Inequity in timing of prenatal screening in New Zealand: Who are our most vulnerable?

In New Zealand (NZ), Maori and Pacific women are less likely to complete prenatal screening for Down syndrome and other aneuploidies than other ethnic groups. Young women <20 have low rates of completed screening compared with women >20 years. Women living in deprived areas have lower completed screen rates than women living in more affluent areas. Combined first trimester screening has a superior sensitivity (85%) compared with second trimester screening (75%) for trisomy 21. The relative contribution of demographic factors to timing of screening uptake (first vs second trimester) has not previously been examined.

Body Mass Index Is Positively Associated with Endometrial Cancer in Chinese Women, Especially Prior to Menopause

Objective: Obesity is a well-known risk factor for developing endometrial cancer. However, the incidence and survival rate of endometrial cancer are associated with ethnicity and geographical area. In addition, whether menopausal status is associated with developing endometrial cancer in obese women and whether obesity is associated with subtypes of endometrial cancer have not been fully investigated. Here, we investigated the effect of BMI on developing endometrial cancer in Chinese women taking into account menopausal status and cancer subtypes. Methods: Data on 1,127 women with endometrial cancer including body mass index (BMI), age at diagnosis, parity, menopausal status and cancer subtype were collected from the largest obstetrics & gynaecology hospital in China and analysed. Results: After adjusting for age and parity, the odds for developing endometrial cancer in overweight or obese perimenopausal women was significantly higher than that in women with normal weight (OR=2.6 with 95%CI:1.9-3.5, and OR=3.5 with 95%CI: 2.2-5.4, respectively). The odds of developing endometrial cancer in overweight postmenopausal women were significantly higher than that in women who were normal weight (OR=2.4 with 95%CI: 1.8-3.1), however this was not the case for obese postmenopausal women. We further found that BMI, menopausal status, age and parity were not associated with subtypes of endometrial cancer. Conclusion: Our data demonstrate that obesity is positively associated with the incidence of developing endometrial cancer in Chinese women, with more significant effects in perimenopausal women.