Obstetrics and Gynaecology - Research Publications
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ItemAccuracy of second trimester prediction of preterm preeclampsia by three different screening algorithms(WILEY, 2018-04)AIM: To compare the performance of three different screening methods (National Institute for Health and Clinical Excellence (NICE) guidelines, American College of Obstetricians and Gynecologists (ACOG) recommendations and Fetal Medicine Foundation (FMF) algorithm) for second trimester prediction of preeclampsia. METHODS: This was a prospective non-intervention study in singleton pregnancies, including women attending for second trimester morphologic ultrasound at 19-22 weeks. Maternal characteristics, medical history, mean arterial pressure and mean uterine artery Doppler pulsatility index were recorded and used for risk assessment. Outcomes measured were preeclampsia with delivery before 34, before 37 and after 37 weeks gestation. Detection rates, false positive rates and positive likelihood ratios were calculated, and receiver operating characteristic curves were produced. RESULTS: We screened 543 women during the study. The incidence of preeclampsia before 34, before 37 and after 37 weeks was 0.5, 1.4 and 3.4%, respectively. Detection rates for prediction of preterm preeclampsia were 75% (95% CI 34.9-96.8), 87% (95% CI 47.3-99.6), 100% (95% CI 63.0-100) and 100% (95% CI 63.0-100) for NICE guidelines, ACOG recommendations, FMF algorithm with a 1:100 cut-off and FMF algorithm at 1:60 cut-off, respectively. False positive rates were, 22, 67, 19 and 12% for NICE guidelines, ACOG recommendations, FMF algorithm with a 1:100 cut-off and FMF algorithm at 1:60 cut-off, respectively. CONCLUSION: Second trimester combined screening for preterm preeclampsia by maternal history, mean arterial pressure and mean uterine artery Doppler pulsatility index (FMF algorithm) was superior to screening by maternal factors alone (NICE guidelines and ACOG recommendations).
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ItemMother Nature versus Father Time(WILEY, 2017-03-15)
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ItemOptic nerve sonography and ophthalmic artery Doppler velocimetry in healthy pregnant women: an Australian cohort study(WILEY, 2019-11)PURPOSE: Maternal ocular sonography offers a window into cerebrovascular and intracranial pressure changes in pregnancy. This study aimed to determine the Doppler velocimetric variables of the ophthalmic artery, and the mean diameter of the optic nerve sheath (ONSD), in an Australian cohort of healthy pregnant women. METHODS: A prospective observational cohort study of healthy women with uncomplicated singleton pregnancies in the third trimester was undertaken in a tertiary maternity service. A single prenatal ultrasonographic examination was performed on all participants, with a postnatal examination performed on a subgroup with uncomplicated deliveries. RESULTS: Fifty women were examined at a mean gestation of 35 weeks. The mean ± SD Doppler variables in the ophthalmic artery were peak systolic velocity (PSV) 41.89 ± 13.13 cm/s, second peak velocity 20.63 ± 8.97 cm/s, end diastolic velocity 9.29 ± 5.13 cm/s, pulsatility index 1.97 ± 0.53, resistive index 0.78 ± 0.07, peak ratio (second peak velocity/PSV) 0.49 ± 0.12, while the mean ONSD was 4.34 ± 0.4 mm. None of these variables had a demonstrable relationship with gestation or mean arterial pressure (MAP), nor did the sheath diameter have a relationship with any of the Doppler variables. CONCLUSIONS: The ocular sonographic variables observed in this population are similar to those reported in other cohorts. No clear relationship could be identified in this cohort between ophthalmic artery Doppler variables and the ONSD, and between each of these variables and gestation or MAP.
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ItemSetting the pace for labour(WILEY, 2018-07-15)
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ItemGenome-Wide Association Scan Identifies a Risk Locus for Preeclampsia on 2q14, Near the Inhibin, Beta B Gene(PUBLIC LIBRARY SCIENCE, 2012-03-14)Elucidating the genetic architecture of preeclampsia is a major goal in obstetric medicine. We have performed a genome-wide association study (GWAS) for preeclampsia in unrelated Australian individuals of Caucasian ancestry using the Illumina OmniExpress-12 BeadChip to successfully genotype 648,175 SNPs in 538 preeclampsia cases and 540 normal pregnancy controls. Two SNP associations (rs7579169, p = 3.58×10(-7), OR = 1.57; rs12711941, p = 4.26×10(-7), OR = 1.56) satisfied our genome-wide significance threshold (modified Bonferroni p<5.11×10(-7)). These SNPs reside in an intergenic region less than 15 kb downstream from the 3' terminus of the Inhibin, beta B (INHBB) gene on 2q14.2. They are in linkage disequilibrium (LD) with each other (r(2) = 0.92), but not (r(2)<0.80) with any other genotyped SNP ±250 kb. DNA re-sequencing in and around the INHBB structural gene identified an additional 25 variants. Of the 21 variants that we successfully genotyped back in the case-control cohort the most significant association observed was for a third intergenic SNP (rs7576192, p = 1.48×10(-7), OR = 1.59) in strong LD with the two significant GWAS SNPs (r(2)>0.92). We attempted to provide evidence of a putative regulatory role for these SNPs using bioinformatic analyses and found that they all reside within regions of low sequence conservation and/or low complexity, suggesting functional importance is low. We also explored the mRNA expression in decidua of genes ±500 kb of INHBB and found a nominally significant correlation between a transcript encoded by the EPB41L5 gene, ∼250 kb centromeric to INHBB, and preeclampsia (p = 0.03). We were unable to replicate the associations shown by the significant GWAS SNPs in case-control cohorts from Norway and Finland, leading us to conclude that it is more likely that these SNPs are in LD with as yet unidentified causal variant(s).
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ItemThe Role of Placental Homeobox Genes in Human Fetal Growth Restriction(HINDAWI LTD, 2011)Fetal growth restriction (FGR) is an adverse pregnancy outcome associated with significant perinatal and paediatric morbidity and mortality, and an increased risk of chronic disease later in adult life. One of the key causes of adverse pregnancy outcome is fetal growth restriction (FGR). While a number of maternal, fetal, and environmental factors are known causes of FGR, the majority of FGR cases remain idiopathic. These idiopathic FGR pregnancies are frequently associated with placental insufficiency, possibly as a result of placental maldevelopment. Understanding the molecular mechanisms of abnormal placental development in idiopathic FGR is, therefore, of increasing importance. Here, we review our understanding of transcriptional control of normal placental development and abnormal placental development associated with human idiopathic FGR. We also assess the potential for understanding transcriptional control as a means for revealing new molecular targets for the detection, diagnosis, and clinical management of idiopathic FGR.
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ItemWomen's Experiences of Preeclampsia: Australian Action on Preeclampsia Survey of Women and Their Confidants(HINDAWI LTD, 2011)INTRODUCTION: The experience of normal pregnancy is often disrupted for women with preeclampsia (PE). MATERIALS AND METHODS: Postal survey of the 112 members of the consumer group, Australian Action on Pre-Eclampsia (AAPEC). RESULTS: Surveys were returned by 68 women (61% response rate) and from 64 (57%) partners, close relatives or friends. Respondents reported experiencing pre-eclampsia (n = 53), eclampsia (n = 5), and/or Hemolysis, Elevated Liver enzymes, and Low Platelets (HELLP syndrome) (n = 26). Many women had no knowledge of PE prior to diagnosis (77%) and, once diagnosed, did not appreciate how serious or life threatening it was (50%). Women wanted access to information about PE. Their experience contributed substantial anxiety towards future pregnancies. Partners/friends/relatives expressed fear for the woman and/or her baby and had no prior understanding of PE. CONCLUSIONS: The PE experience had a substantial effect on women, their confidants, and their babies and affected their approach to future pregnancies. Access to information about PE was viewed as very important.
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ItemDecreased Seizure Threshold in an Eclampsia-Like Model Induced in Pregnant Rats with Lipopolysaccharide and Pentylenetetrazol Treatments(PUBLIC LIBRARY SCIENCE, 2014-02-20)OBJECTIVE: Eclampsia is a poorly understood but potentially fatal complication of pregnancy. Research to date on this disorder has been hampered by the lack of a suitable animal model. To correct this deficiency, this report describes the generation of a rat eclampsia-like model using pentylenetetrazol (PTZ) in a previously established rat preeclampsia model. METHOD: Rats were administered lipopolysaccharide (1.0 µg/kg) by tail vein injection on gestational day 14 to establish preeclampsia (PE). PE and control rats (non-pregnant, NP; normal-pregnant, P) were injected intraperitoneally (i.p.) with PTZ (40 mg/kg) to induce seizures. In separate experiments, MgSO4 (270 mg/kg IP) was injected in advance of PTZ into PE rats to observe its effect on PTZ-induced seizures. RESULTS: PE conditions were verified in rats after LPS administration by significantly higher blood pressure (P<0.01) and urinary albumin excretion (P<0.05), elevated sFlt-1 (P<0.05) and decreased PlGF serum levels (P<0.05), and evidence of hepatic dysfunction compared to control groups. PTZ successfully induced seizure activity in all groups studied. Latency to seizure was significantly (P<0.01) less in the PE-PTZ group (73.2 ± 6.6 sec.) than in PTZ-treated controls (107.0 ± 7.4 sec.). Pretreatment with MgSO4 prolonged (P<0.05) latency to seizure, shortened seizure duration and decreased seizure rates. Significant increased (P<0.05) in the serum levels of the inflammatory cytokines TNF-α and IL-1β in PE and PE-PTZ groups, and decreased (P<0.05) in their levels following MgSO4 administration. CONCLUSION: This PTZ-induced eclampsia-like rat model is comparable to the human condition of eclampsia and may serve as a useful research tool for future studies of this disease. The increased inflammatory cytokines in preeclampsia are coincident with a decreased threshold for PTZ-induced seizures, suggesting that an inflammatory mechanism may contribute to the susceptibility to seizure activity and inflammation might have an important role in eclampsia.