A summary of the 2023 Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) hypertension in pregnancy guideline.

INTRODUCTION: Hypertensive disorders of pregnancy (HDP) affect up to 10% of all pregnancies annually and are associated with an increased risk of maternal and fetal morbidity and mortality. This guideline represents an update of the Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) guidelines for the management of hypertensive disorders of pregnancy 2014 and has been approved by the National Health and Medical Research Council (NHMRC) under section 14A of the National Health and Medical Research Council Act 1992. In approving the guideline recommendations, NHMRC considers that the guideline meets NHMRC's standard for clinical practice guidelines. MAIN RECOMMENDATIONS: A total of 39 recommendations on screening, preventing, diagnosing and managing HDP, especially preeclampsia, are presented in this guideline. Recommendations are presented as either evidence-based recommendations or practice points. Evidence-based recommendations are presented with the strength of recommendation and quality of evidence. Practice points were generated where there was inadequate evidence to develop specific recommendations and are based on the expertise of the working group. CHANGES IN MANAGEMENT RESULTING FROM THE GUIDELINE: This version of the SOMANZ guideline was developed in an academically robust and rigorous manner and includes recommendations on the use of combined first trimester screening to identify women at risk of developing preeclampsia, 14 pharmacological and two non-pharmacological preventive interventions, clinical use of angiogenic biomarkers and the long term care of women who experience HDP. The guideline also includes six multilingual patient infographics which can be accessed through the main website of the guideline. All measures were taken to ensure that this guideline is applicable and relevant to clinicians and multicultural women in regional and metropolitan settings in Australia and New Zealand.

Validation of self-applied unattended polysomnography using Somte V2 PSG (Somte) for diagnosis of obstructive sleep apnoea (OSA) in pregnant women in early to mid-gestation.

PURPOSE: Polysomnography (PSG) may be completed in the home environment (unattended), and when self-applied, allow the collection of data with minimal healthcare worker intervention. Self-applied, unattended PSG in the home environment using Somte PSG V2 (Somte) has not been validated in pregnant women in early to mid-gestation. We undertook a study to evaluate the accuracy of Somte compared to attended PSG. The agreement between apnoea hypopnea index (AHI) and respiratory disturbance index (RDI) scores in Somte and PSG in early to mid-gestation were assessed. METHODS: Pregnant women (≤ 24 weeks gestation) were scheduled for PSG and Somte within a 7-day window, in any order. Somte were self-applied and completed in the home. Somte were scored blinded to PSG result. AHI was the primary outcome of interest, though an AHI ≥ 5 or RDI ≥ 5 on PSG was considered diagnostic of Obstructive Sleep Apnoea (OSA). AHI, RDI, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) was calculated and receiver operating characteristic (ROC) curves were produced. Bland-Altman plots were used to determine agreement. Technical issues occurring during tests were explored. RESULTS: Twenty-four participants successfully completed both tests between March 2021 and January 2023. PSG were completed at around 14.1 weeks' gestation (IQR 13.4, 15.7). The time interval between Somte and PSG was a median of 4 days (IQR 2, 7 (range 1-12)). Five (20.8%) women had OSA on PSG at AHI ≥ 5 and 10 (41.6%) women had OSA on PSG at RDI ≥ 5. Somte and PSG did not differ in the measurement of AHI ((1.8, 1.6, p = 0.09) or RDI (3.3, 3.5), p = 0.73). At AHI ≥ 5, diagnostic test accuracy (area under the ROC curve) of Somte was 0.94, sensitivity 80.0%, specificity 94.7%, PPV and NPV were 80.0% and 94.7% respectively. At RDI ≥ 5, diagnostic test accuracy (area under the ROC curve) was 0.95, sensitivity 60.0%, specificity 93.0% and PPV and NPV were 85.7% and 76.4% respectively. The confidence limits of Bland-Altman plots were 6.37 to - 8.89 at cut off AHI ≥ 5 and 8.89 to - 10.43 at cut off RDI ≥ 5. Somte failed to start in four tests. Technical issues were reported in both Somte (n = 13, 54.2%) and PSG (n = 6, 25.0%). CONCLUSION: Self-applied, unattended Somte may provide an acceptable substitute to attended PSG in the identification of OSA in pregnant women in early to mid-gestation in this small sample but may fail to detect cases of OSA, particularly when using RDI as the diagnostic marker.

Patients and health care workers perceived challenges in managing preeclampsia, in Malawi.

OBJECTIVES: This study investigated perceptions of the challenges for patients and health care workers (HCW) in dealing with preeclampsia in Blantyre, Malawi. METHODS: A descriptive cross-sectional formative study using semi-structured In-Depth Interviews (IDI) was conducted at Queen Elizabeth Central Hospital (QECH), Malawi. Data was analyzed using NVIVO™ software. Thematic content analysis was used to analyze and interpret the findings. Emerging themes were then developed inductively and deductively. Patients were interviewed who recently had preeclampsia. RESULTS: Stress, lack of information, physical symptoms, delay in receiving care were identified challenges to better care among patients as well as the impact of poor pregnancy outcomes. Late diagnosis, staff burn out, inadequate skills and lack of resources were expressed as challenge to provide better management by the interviewed HCWs. CONCLUSION: Our study showed that a diagnosis of preeclampsia is challenging to both patients and HCWs. These challenges need to be addressed carefully at all levels for optimal management of preeclampsia in Malawi, Africa and in order to improve outcomes.

Validation of the Apnealink Air for diagnosis of obstructive sleep apnoea (OSA) in pregnant women in early-mid gestation.

PURPOSE: The detection of obstructive sleep apnoea (OSA) in pregnant women in early-mid gestation is logistically difficult. Accurate alternates to polysomnography (PSG) in early pregnancy are not well identified. We compared the agreement between Apnealink Air (AL) and existing screening questionnaires to PSG in pregnant women ≤ 24-week gestation. METHODS: Pregnant women (≤ 24-week gestation) underwent AL at home plus attended PSG in any order, completed within 7 days where practicable. AL was manually scored (AL(M)) and automatically scored (AL(A)). An apnoea-hypopnea index (AHI) ≥ 5 was considered diagnostic of OSA and an AHI ≥ 15 considered at least moderate OSA. Diagnostic analysis was undertaken (sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV)) by generating receiver operating characteristic (ROC) curves and an area under the curve (AUC) (95% CI). Bland-Altman plots were used to plot agreement. Screening questionnaires (Epworth sleepiness score (ESS), STOP-BANG, calculated pregnancy-specific screening tool) were compared to PSG. RESULTS: A total of 49 participants successfully completed both tests at around 14-weeks gestation (IQR 12.9, 17.1). The time interval between AL and PSG was a median of 2 days (IQR 1, 5 (range 1-11)). A total of 14 (29%) participants had OSA. The median AHI of AL(A) (3.1(IQR 0.85,4.6)) and AL(M) (IQR2.4(0.65,4.8)) did not differ from PSG (1.7(IQR1.0,6.1)). AL(A) and AL(M) compared to PSG demonstrated diagnostic test accuracy (area under curve (ROC)) of 0.94(95% CI 0.87-1.0) and 0.92(95% CI 0.85-1.0) respectively. Apnealink Air outperformed screening questionnaires tested. CONCLUSION: The findings suggest that Apnealink may provide a substitute to attended PSG identification of OSA in pregnant women in early-mid gestation using both manual and auto-scoring methods.

Remote blood pressure monitoring in high risk pregnancy - study protocol for a randomised controlled trial (REMOTE CONTROL trial).

BACKGROUND: Pregnant women at high risk for developing a hypertensive disorder of pregnancy require frequent antenatal assessments, especially of their blood pressure. This expends significant resources for both the patient and healthcare system. An alternative to in-clinic assessments is a remote blood pressure monitoring strategy, in which patients self-record their blood pressure at home using a validated blood pressure machine. This has the potential to be cost-effective, increase patient satisfaction, and reduce outpatient visits, and has had widespread uptake recently given the increased need for remote care during the ongoing COVID-19 pandemic. However robust evidence supporting this approach over a traditional face-to-face approach is lacking, and the impact on maternal and foetal outcomes has not yet been reported. Thus, there is an urgent need to assess the efficacy of remote monitoring in pregnant women at high risk of developing a hypertensive disorder of pregnancy. METHODS: The REMOTE CONTROL trial is a pragmatic, unblinded, randomised controlled trial, which aims to compare remote blood pressure monitoring in high-risk pregnant women with conventional face-to-face clinic monitoring, in a 1:1 allocation ratio. The study will recruit patients across 3 metropolitan Australian teaching hospitals and will evaluate the safety, cost-effectiveness, impact on healthcare utilisation and end-user satisfaction of remote blood pressure monitoring. DISCUSSION: Remote blood pressure monitoring is garnering interest worldwide and has been increasingly implemented following the COVID-19 pandemic. However, robust data regarding its safety for maternofoetal outcomes is lacking. The REMOTE CONTROL trial is amongst the first randomised controlled trials currently underway, powered to evaluate maternal and foetal outcomes. If proven to be as safe as conventional clinic monitoring, major potential benefits include reducing clinic visits, waiting times, travel costs, and improving delivery of care to vulnerable populations in rural and remote communities. TRIAL REGISTRATION: The trial has been prospectively registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12620001049965p, on October 11th, 2020).

Health care workers and key policy informant's knowledge of the use of calcium and low dose aspirin for prevention of preeclampsia in Malawian women.

OBJECTIVES: This study investigated health care workers and key policy informant's knowledge, and barriers to the use of calcium and aspirin for preventing preeclampsia in Blantyre and Lilongwe, Malawi. METHODS: A descriptive cross-sectional formative study using semi-structured In-Depth Interview (IDIs) was conducted at Queen Elizabeth Central Hospital (QECH), Reproductive Health Directorate, and the United Nations Population Development Fund (UNFPA) Office in 2021. Data was analyzed using NVIVO™ software. Thematic content analysis was used to analyze and interpret the findings. Emerging themes were then developed inductively and deductively. RESULTS: Doctors had greater knowledge of the use of calcium and aspirin for prevention of preeclampsia compared to nurses and key policy informants. Lack of knowledge, patient's late presentation, scarcity of calcium tablets and delays in implementing new guidelines were the barriers to use identified. CONCLUSION: This study shows that there are health care worker and policy level barriers that affect the implementation of calcium and aspirin use for the prevention of preeclampsia in Malawian women.

Prevalence of long term metabolic, cardiovascular, cerebrovascular and renal disease in patients with hypertensive disorders in pregnancy remote from pregnancy (POMCH).

BACKGROUND: Hypertensive disorders of pregnancy (HDP) are associated with an increased risk of long-term cardiovascular, cerebrovascular, and adverse renal outcomes. Biomarkers including soluble fms-like tyrosine kinase 1 (sFlt1), placental growth factor (PlGF) are predictive of the development of preeclampsia. Their long-term value in predicting which women will develop cardiovascular complications remote from pregnancy is not yet established. OBJECTIVES: To determine the prevalence and incidence of Cardio-renal-metabolic outcomes at 10 years follow-up in a cohort of women screened for suspected preeclampsia from 2008 to 2009 and assess the relationship between pregnancy biomarkers and long-term outcomes. STUDY DESIGN: A retrospective cohort study of 117 women. Outcomes were assessed by auditing medical records. The primary outcome was the prevalence of cardiovascular, cerebrovascular, metabolic and renal outcomes at 10 years remote from the diagnosis of HDP. The secondary outcome was to assess the relationship of the remote from pregnancy outcomes to biomarkers (sFlt1, PlGF, soluble endoglin (sEng) and neutrophil gelatinase associated lipocalin (NGAL)) taken at the time of pregnancy comparing the results of those with adverse outcomes compared to those without. RESULTS: There was a 12.7% prevalence of cardiovascular and cerebrovascular disease, 44.4% prevalence of hypertension, 20.6% prevalence of chronic kidney disease and 17.5% prevalence of diabetes. Women who developed preeclampsia had an increased prevalence and incidence of adverse outcomes compared to women without preeclampsia. There was a weak relationship between sENg measured at the time of clinical suspicion of preeclampsia and the adverse outcomes 144 (139-146) months remote from pregnancy. CONCLUSIONS: Biomarkers taken at the time of pregnancy did not accurately predict the long-term adverse cardiometabolic outcomes.

Assessment and Management of Primary Aldosteronism in Pregnancy: A Case-Control Study.

CONTEXT: Primary aldosteronism (PA) is a common secondary cause of hypertension. Literature regarding PA in pregnancy has demonstrated poor outcomes. OBJECTIVE: Compare the management and outcomes of PA in pregnancy to both high and low-risk matched controls. METHODS: This was a case-control trial conducted in a network of metropolitan hospitals in Sydney, Australia. PA women (positive salt suppression test) with singleton pregnancies delivered after 20 weeks' gestation were matched to women with high- and low-risk pregnancies. Management outcomes included pre-eclampsia prophylaxis and antihypertensive medications required prenatally, antenatally, and postnatally. Maternal outcomes included incidence of pre-eclampsia, gestational diabetes, hypokalemia, mode of delivery, and length of stay postpartum. Neonatal outcomes included gestation, birthweight, intensive care unit admission, and length of stay. RESULTS: Fifty-nine women with 60 pregnancies were included (20 PA, 20 high risk, and 20 low risk). The number of antihypertensive medications women with PA took prepregnancy was similar to the high-risk group. A similar proportion of women in the PA and high-risk groups were prescribed pre-eclampsia prophylaxis and developed pre-eclampsia. Even after adjustment for several factors, PA was not independently associated with pre-eclampsia development. Women with PA had higher antihypertensive requirements and a longer stay in hospital postpartum than the high-risk group (both P = .02). There was no difference in neonatal adverse outcomes. Four women took epleronone during pregnancy without any adverse effects noted. CONCLUSION: Women with PA required more antihypertensives and had a longer postpartum length of stay than matched high-risk women, but similar rates of pre-eclampsia. There was no difference in the rate of neonatal intensive care admissions or adverse outcomes for neonates.

The 15-Epilipoxin-A4 Pathway with Prophylactic Aspirin in Preventing Preeclampsia: A Longitudinal Cohort Study.

INTRODUCTION: The benefit of aspirin in preventing preeclampsia is increasingly recognized; however, its mechanism of action remains unclear. Nonobstetric studies have described an anti-inflammatory effect of aspirin through the 15-epilipoxin-A4 pathway (aspirin-triggered lipoxin [ATL]). However, the anti-inflammatory mechanism of aspirin in the prevention of preeclampsia remains unknown. OBJECTIVE/HYPOTHESIS: To examine (1) the difference in longitudinal endogenous lipoxin-A4 (En-Lipoxin-A4) concentration in low-risk (LR) and high-risk (HR) pregnancies, and (2) the effect of aspirin on endogenous ATL concentration and the associated effect on cytokine profile of HR women. METHODS: Plasma from 220 HR women was collected at 12, 16, 20, 24, 28, 32, and 36 weeks of gestation. Adherence to aspirin was biochemically verified. Plasma En-Lipoxin-A4 and ATL concentrations were analyzed using liquid chromatography mass spectrometry, and cytokines, interleukin (IL)-10, tumor necrosis factor-α, interferon-γ, IL-8, and IL-1ß, with the high-sensitivity multibead Luminex® assay. RESULTS: HR women have up to 70% lower plasma concentration of En-Lipoxin-A4 (P < 0.001) than LR women. HR women with adequate aspirin adherence (HR-AA) (n = 82) had higher plasma concentration of ATL (P < .001), lower concentration of IL-8 from 16 to 36 weeks of gestation (P < .001), and increased IL-10 concentration from 16 to 28 weeks of gestation (P = .03) compared with high-risk women who were not on aspirin (HR-NA). HR-AA who did not develop preeclampsia had higher plasma En-lipoxin-A4 (P < .001), ATL (P = .02), and IL-10 concentrations (P < .001) with lower IL-8 concentration (P = .004) than HR women who developed preeclampsia. DISCUSSION: Plasma concentration of En-Lipoxin-A4 is lower in HR women than in LR controls. Adequate adherence with aspirin results in an increase in ATL and IL-10 with reduced IL-8 plasma concentration. This study suggests a potential anti-inflammatory role of aspirin through the ATL pathway with prophylactic aspirin in HR pregnant women.

Galectin-1-Related Modulation of Trophoblast Endothelial Interactions by Integrins α1 and ß1.

During normal trophoblast invasion, integrins α6ß4 are downregulated, and α1ß1 are upregulated in invasive cytotrophoblast cells. In preeclampsia both interstitial and endovascular invasion are shallow and cytotrophoblasts fail to upregulate α1ß1 and downregulate α6ß4. This study aims to investigate the role of integrins α1ß1 and α6ß4 on cellular pathways influencing trophoblast integration into endothelial cellular networks in vitro. Red fluorescent-labeled human uterine myometrial microvascular endothelial cells (UtMVECs) were seeded on Matrigel to form endothelial networks. Green fluorescent-labeled trophoblastic HTR-8/SVneo cells pre-incubated with 20 µg/ml of neutralizing antibodies (anti-α1, ß1, α6, ß4, α1 + ß1, or α6 + ß4) for 1 h were then co-cultured with endothelial networks with the neutralizing antibodies for 24 h. Fluorescent images were captured, and quantified utilizing Image J. Cells were retrieved to analyze mRNA expression of galectin-1, TIMP-1, and PAI-1 by quantitative PCR. MMP-2, MMP-9, free sFlt-1, and PlGF from conditioned media were measured by ELISA. The integration of trophoblast cells into endothelial cellular networks was inhibited by anti-ß1(- 28 ± 3%, p < 0.0001), and increased by anti-α6(+ 19 ± 5%, p < 0.01). Galectin-1 mRNA expression was decreased by anti-α1(- 35 ± 7%, p < 0.001), anti-ß1(- 23 ± 5%, p < 0.05), and anti-α1+ß1(- 35 ± 5%, p < 0.001). The mRNA expression of TIMP-1 was inhibited by anti-α1(- 59 ± 9%, p < 0.01) and anti-ß1(- 63 ± 7%, p < 0.001) while PAI-1 mRNA expression was increased by anti-α1 + ß1(+ 285 ± 70%, p < 0.0001). In the conditioned medium, anti-α1 reduced MMP-2(-28 ± 1%, p < 0.001), MMP-9(-27 ± 8%, p < 0.01), and sFlt-1(-27 ± 5%, p < 0.001) production. Anti-ß1 reduced MMP-2(- 15 ± 2%, p < 0.05) production. There were no changes in PlGF. Appropriate integrins α1ß1 modulate trophoblast cell integration into endothelial cellular networks in vitro through invasive pathways including galectin-1, TIMP-1, PAI-1, MMP-2, and MMP-9 production.

Clinical Influence of Nonadherence With Prophylactic Aspirin in Preventing Preeclampsia in High-Risk Pregnancies: A Multicenter, Prospective, Observational Cohort Study.

Aspirin nonadherence and its associated increase in cardiovascular and cerebrovascular events is well described; however, the prevalence of aspirin nonadherence among high-risk pregnant women at risk of preeclampsia and its influence on clinical outcomes remains unclear. Our study examined the prevalence of aspirin nonadherence and resistance among high-risk pregnant women quantitatively (platelet function analyzer 100 and plasma salicylic acid) and clinical outcomes relative to adherence. High-risk pregnant women were recruited across 3 centers in the South West Sydney Local Health District. Simultaneous clinic data, blood sample, and self-reported adherence assessment were prospectively collected at 4-week intervals from 12 to 36 weeks of gestation. Nonadherence was defined as normal platelet function analyzer 100 and nondetectable plasma salicylic acid in <90% of time points. Value of <90% is based on current data. Two hundred twenty women were recruited over 25 months. No woman was aspirin resistant, and 63 (44%) women demonstrated inadequate adherence. Women with inadequate adherence had higher incidence of early-onset preeclampsia (17% versus 2%; odds ratio [OR], 1.9 [95% CI, 1.1-8.7]; P=0.04), late-onset preeclampsia (41% versus 5%; OR, 4.2 [95% CI, 1.4-19.8]; P=0.04), intrauterine growth restriction (29% versus 5%; OR, 5.8; [95% CI, 1.2-8.3]; P=0.001), preterm delivery (27% versus 10%; OR, 5.2 [95% CI, 1.5-8.7]; P=0.008), and higher likelihood of increase in antihypertensives antenatally (60% versus 10%; OR, 4.6 [95% CI, 1.2-10.5]; P=0.003). Kaplan-Meier analysis demonstrated lower incidence of premature delivery in the ≥90% adherent group (HR, 0.3 [95% CI, 0.2-0.5]; P<0.001).Kappa coefficient agreement between qualitative and quantitative assessment of adherence was moderate (κ=0.48; SE=0.029; P<0.0001). Our data demonstrates that aspirin is an effective prophylactic agent with an absolute risk reduction of 51% (number needed to treat, 2) when adherence is ≥90%, compared with women with inadequate adherence. Women who were <90% adherent had higher rates of preeclampsia, intrauterine growth restriction, preterm delivery, and increase in antenatal antihypertensive requirements. Self-reported adherence does not accurately reflect actual adherence.

Factors that influence adherence to aspirin therapy in the prevention of preeclampsia amongst high-risk pregnant women: A mixed method analysis.

BACKGROUND: Non-adherence with medications in pregnancy is increasingly recognized and often results in a higher rate of preventable maternal and fetal morbidity and mortality. Non-adherence with prophylactic aspirin amongst high-risk pregnant women is associated with higher incidence of preeclampsia, preterm delivery and intrauterine growth restriction. Yet, the factors that influences adherence with aspirin in pregnancy, from the women's perspective, remains poorly understood. OBJECTIVE: The study is aimed at understanding the factors, from the women's perspective, that influenced adherence with prophylactic aspirin in their pregnancy. STUDY DESIGN: A sequential-exploratory designed mixed methods quantitative (n = 122) and qualitative (n = 6) survey of women with recent high-risk pregnancy necessitating antenatal prophylactic aspirin was utilized. Women recruited underwent their antenatal care in one of three high-risk pregnancy clinics within the South Western Sydney Local Health District, Australia. The quantitative study was done through an electronic anonymous survey and the qualitative study was conducted through a face-to-face interview. Data obtained was analysed against women's adherence with aspirin utilizing phi correlation (φ) with significance set at <0.05. RESULTS: Two key themes, from the women's perspective, that influenced their adherence with aspirin in pregnancy were identified; (1) pill burden and non-intention omission (2) communication and relationship with health care provider (HCP). Pill burden and its associated non-intentional omission, both strongly corelated with reduced adherence (Φ = 0.8, p = 0.02, Φ = 0.8, p<0.01) whilst the use of reminder strategies minimized accidental omission and improved adherence (Φ = 0.9, p<0.01). Consistent communication between HCPs and a good patient-HCP relationship was strongly associated with improved adherence (Φ = 0.7, p = 0.04, Φ = 0.9, p = <0.01) and more importantly was found to play an important role in alleviating factors that had potentials to negatively influence adherence with aspirin in pregnancy. CONCLUSION: This study identified factors that both positively and negatively influenced adherence with aspirin amongst high-risk pregnant women. Is highlights the importance in recognizing the impact of pill burden in pregnancy and the need to counsel women on the utility of reminder strategies to minimize non-intentional omission. Importantly, it emphasizes on the importance of a positive patient-HCP relationship through effective and consistent communication to achieve the desired maternal and fetal outcomes.

A pharmacokinetic assessment of optimal dosing, preparation, and chronotherapy of aspirin in pregnancy.

BACKGROUND: The benefit of aspirin in preventing preeclampsia is well established; however, studies over the years have demonstrated variability in outcomes with its use. Potential contributing factors to this variation in efficacy include dosing, time of dosing, and preparation of aspirin. OBJECTIVE: We aimed to compare the difference in pharmacokinetics of aspirin, through its major active metabolite, salicylic acid, in pregnant women and nonpregnant women, and to examine the effect of dose (100 mg vs 150 mg), preparation (enteric coated vs non-enteric-coated), and chronotherapy of aspirin (morning vs evening) between the 2 groups. MATERIALS AND METHODS: Twelve high-risk pregnant women and 3 nonpregnant women were enrolled in this study. Pregnant women were in 1 of 4 groups (100 mg enteric coated, 100 mg non-enteric-coated, 150 mg non-enteric-coated morning dosing, and 150 mg non-enteric-coated evening dosing), whereas nonpregnant women undertook each of the 4 dosing schedules with at least a 30-day washout period. Blood samples were collected at baseline (before ingestion) and at 1, 2, 4, 6, 12, and 24 hours after ingestion of aspirin. Plasma obtained was analyzed for salicylic acid levels by means of liquid chromatography-mass spectrometry. Pharmacokinetic values of area under the curve from time point 0 to 24 hours point of maximum concentration, time of maximum concentration, volume of distribution, clearance, and elimination half-life were analyzed for statistical significance with SPSS v25 software. RESULTS: Pregnant women had a 40% ± 4% reduction in area under the curve from time point 0 to 24 hours (P < .01) and 29% ± 3% reduction in point of maximum concentration (P < .01) with a 44% ± 8% increase in clearance (P < .01) in comparison to that in nonpregnant women when 100 mg aspirin was administered. The reduction in the area under the curve from time point 0 to 24 hours, however, was minimized with the use of 150 mg aspirin in pregnant women, with which the area under the curve from time point 0 to 24 hours was closer to that achieved with the use of 100 mg aspirin in nonpregnant women. There was a 4-hour delay (P < .01) in the time of maximum concentration, a 47% ± 3% reduction in point of maximum concentration (P < .01) and a 48% ± 1% increase in volume of distribution (P < .01) with the use of 100 mg enteric-coated aspirin compared to non-enteric-coated aspirin, with no difference in the overall area under the curve. There was no difference in the pharmacokinetics of aspirin between morning and evening dosing. CONCLUSION: There is a reduction in the total drug metabolite concentration of aspirin in pregnancy, and therefore a dose adjustment is potentially required in pregnant women. This is likely due to the altered pharmacokinetics of aspirin in pregnancy, with an increase in clearance. There was no difference in the total drug metabolite concentration of aspirin between enteric-coated and non-enteric-coated aspirin and between morning and evening dosing of aspirin. Further pharmacodynamic and clinical studies are required to examine the clinical relevance of these pharmacokinetic findings.

Aspirin in the prevention of preeclampsia: the conundrum of how, who and when.

Aspirin is widely used in preventing early onset preeclampsia in women who are identified as being high risk. Although the benefit of aspirin is increasingly evident and acknowledged, there remains many unanswered questions with regards to its optimal application in pregnancy. The issues mainly centre around the relatively modest risk reduction that is observed with the use of aspirin prophylactically. We aim to explore the reasons behind the conservative rate of benefit and aim to explore factors that are likely to influence the outcomes with the use of aspirin.

RNAi modulation of placental sFLT1 for the treatment of preeclampsia.

Preeclampsia is a placentally induced hypertensive disorder of pregnancy that is associated with substantial morbidity and mortality to mothers and fetuses. Clinical manifestations of preterm preeclampsia result from excess circulating soluble vascular endothelial growth factor receptor FLT1 (sFLT1 or sVEGFR1) of placental origin. Here we identify short interfering RNAs (siRNAs) that selectively silence the three sFLT1 mRNA isoforms primarily responsible for placental overexpression of sFLT1 without reducing levels of full-length FLT1 mRNA. Full chemical stabilization in the context of hydrophobic modifications enabled productive siRNA accumulation in the placenta (up to 7% of injected dose) and reduced circulating sFLT1 in pregnant mice (up to 50%). In a baboon preeclampsia model, a single dose of siRNAs suppressed sFLT1 overexpression and clinical signs of preeclampsia. Our results demonstrate RNAi-based extrahepatic modulation of gene expression with nonformulated siRNAs in nonhuman primates and establish a path toward a new treatment paradigm for patients with preterm preeclampsia.

Pregnancy-induced atypical haemolytic uremic syndrome: A new era with eculizumab.

Pregnancy is a well-recognised trigger of atypical haemolytic syndrome (P-aHUS) and often occurs in the post-partum period. Similar to atypical haemolytic uremic syndrome, it carries a poor prognosis with high morbidity particularly in the form of renal failure. Early recognition and intervention is crucial in its management particularly with the recent availability of eculizumab, a humanized monoclonal antibody to complement component C5, which has demonstrated drastic improvement in prognosis. The issue, however, is arriving at a timely diagnosis given the considerable amount of overlap in the clinical and biochemical manifestation of P-aHUS, HELLP syndrome (haemolysis, elevated liver enzyme and low platelet count) and other hypertensive disorders of pregnancy. We present a case report and literature review that highlights the clinical conundrum of arriving at the diagnosis. We also highlight the importance of early management of P-aHUS with eculizumab and its impact on improving morbidity.

The effect of acetyl salicylic acid (Aspirin) on trophoblast-endothelial interaction in vitro.

Early administration of low dose acetyl salicylic acid (Aspirin) in high risk women reduces the risk of early onset preeclampsia. This study aims to investigate the effect of aspirin on trophoblast integration and the its effect on angiogenic and invasive pathways in an in-vitro model of preeclampsia. Red fluorescent-labeled human uterine myometrial microvascular endothelial cells (UtMVECs) were seeded on matrigel to form endothelial networks. Green fluorescent-labeled trophoblastic HTR-8/SVneo cells were co-cultured with the endothelial networks with/without TNF-a (0.5ng/mL) and/or aspirin (0.1mM) for 24h. Fluorescent images were captured and quantified by Image J to examine the effects of TNF-a and aspirin on the trophoblast-endothelial integration. Conditioned media were collected to measure free VEGF, PlGF and sFlt-1 by ELISA and PGF1a by Enzyme immunoassay (EIA). Cells were retrieved to examine mRNA expression of angiogenic factors (VEGF, PlGF and sFlt-1), invasion markers (MMP-2 and TIMP-1), endothelial cell activation markers (E-selectin and VCAM), eNOS and cyclooxygenase (COX)-2 by quantitative PCR. Aspirin reversed the inhibitory effect of TNF-a on trophoblast cell integration into endothelial cellular networks. TNF-a increased PGF1a production (128±11%, p<0.05), whilst aspirin reversed the TNF-a effect on PGF1a production (19±4%, p<0.01). TNF-a decreased the mRNA expression of PlGF, eNOS, MMP-2 and TIMP-1, and stimulated COX2, E-selectin and VCAM mRNA expression. Aspirin did not reverse the TNF-a effect on these molecules. Aspirin improves trophoblast cell integration into endothelial cellular networks by inhibiting the effect of TNF-a via PGI2 with no significant effect on antiangiogenic, invasive or endothelial activation markers.

The Utility of Sonographic Assessment in Selecting Patients for Percutaneous Insertion of Peritoneal Dialysis Catheter.

BACKGROUND: Percutaneous insertion of peritoneal dialysis (PD) catheters by nephrologists is a safe and effective alternative to open surgical techniques. These patients are usually carefully selected due to anatomical considerations and medical comorbidities, with the current literature suggesting exclusion of patients with prior abdominal surgery. METHOD: We conducted a retrospective cohort study of pre-dialysis patients who attended a preprocedural clinic in a tertiary center over 6 years. Procedural complications and catheter survival were assessed. Chi-squared test and Kaplan-Meier survival analysis were undertaken. Inpatient assessments were excluded. RESULTS: A total of 217 patients were assessed, of whom 171 (78.8%) were accepted for percutaneous PD catheter insertion by a nephrologist. The key exclusion criteria were: (1) the clinical presence of abdominal hernia (p < 0.001), (2) ultrasound findings of skin to peritoneum depth of > 5.5 cm (p < 0.001) and (3) ultrasound findings of impaired visceral slide test (p < 0.001). Prior abdominal surgery was not a default exclusion criterion (p = 0.1), as 63 patients (37%) with prior abdominal surgery, average of 1.3 prior surgeries per patient, were assessed as appropriate for the percutaneous procedure. There was no difference in the procedural complication rate and catheter survival between patients with and without prior abdominal surgery. CONCLUSION: A comprehensive preprocedural assessment utilizing ultrasound permits an objective selection of patients for percutaneous insertion of PD catheters by nephrologists. This allowed for successful and safe percutaneous insertion of PD catheters in patients who may have otherwise been excluded, e.g., prior abdominal surgery, patients with large bilateral polycystic kidneys, and central obesity.

Vertebral artery dissection in hypertensive disorders of pregnancy: a case series and literature review.

BACKGROUND: Arterial dissection is a rare complication of pregnancy and puerperium. There have been reports of aortic, coronary and cervical artery dissection in association with preeclampsia, however, vertebral artery dissection is rarely reported particularly in the antenatal setting in the presence of a Hypertensive Disorder of Pregnancy (HDP).The general annual incidence of symptomatic spontaneous cervicocephalic arterial dissection is 0.0026 % and a data registry reported that 2.4 % of these occurred in the post-partum period. The actual incidence of vertebral artery dissection in HDP is unknown as the current literature consists of case series and reports only with most documenting adverse outcomes. Given the presence of collateral circulation, unilateral vertebral artery dissections may go unrecognised and may be more common than suspected. CASE PRESENTATION: We present a case series of four patients with vertebral artery dissection in association with HDP, two of which occurred in the antenatal setting and two in the post-partum setting. All our patients had favourable outcome with no maternal neurological deficit and live infants. Our discussion covers the proposed pathophysiology of vertebral artery dissection in HDP and the management of it. CONCLUSION: Our case series highlights the need to consider VAD an important differential diagnosis when assessing pregnant women with headache and neck pain particularly in the context of HDP.