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.

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.

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.

Short communication: Where is women's cardiovascular health taught in Australian and New Zealand medical schools?

Cardiovascular disease is a major cause of mortality in women and is the leading cause of pregnancy-related mortality in Australia. This study aims to discover the extent of teaching regarding women's cardiovascular health in Australian and New Zealand medical schools. All 22 medical schools in Australia and New Zealand were approached for participation in completing this survey. Seven medical schools (32%) completed the survey and demonstrated that within our sample population, findings suggest that while women's cardiovascular health is present in medical curricula, there is a large variability in the rigour and depth as to which it is taught, as well as possible lack of explicit teaching and examination regarding this topic.

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).

A hidden problem: peripheral artery disease in women.

Peripheral artery disease (PAD) has a huge social and economic burden and is an important contributor to the global health burden. Sex differences in PAD are apparent, with recent data suggesting equal if not greater prevalence in women, and women having worse clinical outcomes. Why this occurs is not clear. To identify underlying reasons for gender inequalities in PAD, we executed a deeper exploration through a social constructive perspective. A scoping review was conducted using the World Health Organization model for analysis of gender-related needs in healthcare. Complex interacting factors, including biological, clinical, and societal variables, were reviewed to highlight gender-related inequities in the diagnosis, treatment, and management of PAD. Current gaps in knowledge were identified and insights into future directions aimed at improving these inequalities were discussed. Our findings highlight the multi-level complexities that need to be considered for strategies to improve gender-related needs in PAD healthcare.

Clinical characteristics and sequelae of intrapartum hypertension - a retrospective cohort study.

BACKGROUND: In a significant proportion of pregnant women, elevated blood pressure may first present during the intrapartum period. This phenomenon, intrapartum hypertension, is often overlooked as blood pressure during delivery is attributed to labour pain, analgesic agents and haemodynamic changes. Thus the true prevalence and clinical significance of intrapartum hypertension remains unknown. This study sought to define the prevalence of intrapartum hypertension in previously normotensive women, identify associated clinical characteristics, and its impact on maternal and fetal outcomes. METHODS: In this single-center retrospective cohort study, all available partograms were reviewed over a 1-month period at an outer metropolitan hospital in Sydney (Campbelltown Hospital). Women with diagnosed hypertensive disorders of pregnancy during the incident pregnancy were excluded. A total of 229 deliveries were included in the final analysis. Intrapatum hypertension (IH) was defined as two or more systolic blood pressure (SBP)⩾140 mmHg or diastolic blood pressure (DBP)⩾90 mmHg during the intrapartum. Demographic data at the time of the first antenatal visit for the incident pregnancy as well as final maternal outcomes (intrapartum and post-partum) and fetal outcomes were collected. Statistical analyses were carried out using SPSSv27 with adjustments for baseline variables. RESULTS: Amongst 229 deliveries, 32 women (14%) had intrapartum hypertension. Older maternal age (p = 0.02), higher body mass index (p < 0.01) and higher diastolic blood pressure at the first antenatal visit (p = 0.03) were associated with intrapartum hypertension. A longer second stage of labour (p = 0.03), intrapartum non-steroidal anti-inflammatory medications (p < 0.01) and epidural anaesthesia (p = 0.03) were associated with intrapartum hypertension, while IV syntocin for labour induction was not. Women with intrapartum hypertension had a longer inpatient admission following delivery (p < 0.01), and elevated postpartum BP (p = 0.02) with discharge on antihypertensive medications (p < 0.01). Intrapartum hypertension was not associated with poor fetal outcomes, though subgroup analyses showed that women who had at least a single elevated blood pressure reading during the intrapartum experienced poorer fetal outcomes. CONCLUSION: In previously normotensive women, 14% developed intrapartum hypertension during delivery. This was associated with postpartum hypertension, longer maternal admission and discharge with antihypertensive medications. There was no difference in fetal outcomes.

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.

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 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice.

All units managing hypertensive pregnant women should maintain and review uniform departmental management protocols and conduct regular audits of maternal & fetal outcomes. The cause(s) of pre-eclampsia and the optimal clinical management of the hypertensive disorders of pregnancy remain uncertain; therefore, we recommend that every hypertensive pregnant woman be offered an opportunity to participate in research, clinical trials and follow-up studies.

Progress in preeclampsia: the contribution of animal models.

Recent advances have been made in understanding the nature of placental dysfunction causing preeclampsia, and other hypertensive disorders of pregnancy. The contribution of animal studies in the understanding of the effects of inadequate placentation on blood pressure and other target organs will be explored in this review. This will include technical aspects of animal studies in pregnancy, as well as the translation of data regarding newly discovered pathological pathways, in particular the angiogenic pathway, into targets in clinical practice.

Blood pressure assessments of pregnant women in a Day Assessment Unit - A prospective observational study.

AIM: We investigated the optimum time and number of observations for assessing women in the Day Assessment Unit. METHODS: A single centre prospective observational study was undertaken. Women referred for blood pressure assessment in the Day Assessment Unit were recruited. RESULTS: The blood pressure of women who subsequently developed preeclampsia was noted to change differently over the time of observation compared to women with other hypertensive disorders, most notably in the first and third hour (p = 0.042), although the averages at each hour did not differ between these two groups. CONCLUSIONS: Mean blood pressure measured over four hours did not significantly differ compared to blood pressure measured over one hour. Women who subsequently developed preeclampsia had a different pattern of blood pressure change whilst in the Day Assessment Unit.

Accuracy of High-Resolution Manometry in Hiatal Hernia Diagnosis in Primary and Revision Bariatric Surgery.

PURPOSE: There is a complex association between obesity, hiatal hernia (HH), and reflux. There is a deficiency of literature on the accuracy of preoperative high-resolution manometry (HRM) in detecting HH before both primary and revision bariatric surgery. MATERIALS AND METHODS: A retrospective analysis of a prospective database of all HRM performed before bariatric surgery from 2014 to 2019. An electronic medical records review was conducted. Sensitivity, specificity, and global diagnostic test accuracy were calculated. RESULTS: Sixty-seven patients with HRM (mean age of 44.0 ± 11.3 years, body mass index 40.8 ± 6.9 kg/m2) were eligible. Intraoperative diagnosis of HH was made in 37 patients (55.2% prevalence). The HRM sensitivity was 48.7% (95% confidence interval (CI) 31.9-65.6%), specificity 90.0% (95% CI 73.5-97.9%), and accuracy was 67.2% (95% CI 54.6-78.2%). Comparing primary (28) and revision (39) surgery, the sensitivity (37.5% vs 57.1%), specificity (75.0% vs 100%), and diagnostic accuracy (54.3% vs 76.3%) were comparable, with overlapping 95% CI. Endoscopy performed in 30 patients had a sensitivity of 25.5% (95% CI 6.8-49.9%), specificity of 100% (95% CI 75.3-100%), and accuracy of 57.8% (95% CI 38.5-75.5%) and was comparable to HRM. CONCLUSION: High-resolution manometry for the detection of HH before bariatric surgery has a high specificity and maintains a high accuracy in both primary and revision bariatric surgery.

The Learning Curves for Transradial and Ultrasound-Guided Arterial Access: An Analysis of the SURF Trial.

INTRODUCTION: Historically, coronary angiography and percutaneous coronary intervention involved accessing the femoral artery via palpation. However, recently there has been a trend towards using a transradial approach and ultrasound guidance for arterial access. Studies have shown that these techniques respectively improve major bleeding rates and access outcomes. There have been no studies conducted that assess the time it takes to train operators to attain proficiency. This sub-analysis of the Standard versus Ultrasound-guided Radial and Femoral access in coronary angiography and intervention (SURF) trial aims to assess the number of procedures required to attain proficiency in ultrasound-guided transradial and transfemoral access. METHODS: The SURF trial randomised 1,388 patients undergoing coronary angiography and/or percutaneous coronary intervention into standard or ultrasound-guidance and radial or femoral access in a 2×2 factorial design. Operators who participated in this trial were required to have performed at least 50 standard and 10 ultrasound-guided punctures for each of transradial and transfemoral access. Cases were then chronologically ordered and stratified into groups of five, from which the primary endpoint measured was a progression in mean access time and first-pass success rates. RESULTS: Across all operators, there was a reduction in mean access time between procedures one to five and six to 10 with ultrasound-guided femoral punctures (60.5 secs-51.5 secs, p=0.029) and between procedures 11 to 15 and 16 to 20 ultrasound-guided radial punctures (74s to 62.5 secs, p=0.082). This trend was more obvious in trainees, with significant reductions in mean access time between procedures one to five and six to 10 from 73.5 to 53.5 seconds (p<0.001) for ultrasound-guided femoral access and from 99.5 seconds to 60 seconds (p=0.024) for ultrasound-guided radial access. There were no trends with standard transradial access. CONCLUSION: The numbers required to attain competency in ultrasound-guided femoral and radial access are 15 and 25 punctures, respectively. Fifty (50) punctures appear adequate for proficiency in a standard transradial approach. These numbers are useful in incorporating into training program for advanced trainees and interventionalists.

A multi-centre, open label, randomised, parallel-group, superiority Trial to compare the efficacy of URsodeoxycholic acid with RIFampicin in the management of women with severe early onset Intrahepatic Cholestasis of pregnancy: the TURRIFIC randomised trial.

BACKGROUND: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-eclampsia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rifampicin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. METHODS: We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rifampicin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. DISCUSSION: Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing "standard" UDCA therapy with rifampicin, and so be able to provide for the first-time high-quality evidence for use of rifampicin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. TRIAL IDENTIFIERS: Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018-004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.

S-glutathionylation of the Na+-K+ Pump: A Novel Redox Mechanism in Preeclampsia.

CONTEXT: Reduced Na+-K+ pump activity is widely reported in preeclampsia and may be caused by a reversible oxidative modification that is a novel pathological feature of preeclampsia. OBJECTIVE: This work aims to determine whether ß 1 subunit (GSS-ß 1) protein glutathionylation of the Na+-K + pump occurs in preeclampsia. METHODS: The GSS-ß1 of the Na+-K+ pump and its subunit expression in human placentas were compared between women with healthy pregnancies and women with preeclampsia. Human placental samples of pregnant women with preeclampsia (n = 11, mean gestational age 36.5 weeks) were used to examine the GSS-ß 1 of the Na+-K+ pump, compared to healthy pregnancies (n = 11, mean gestational age 39 weeks).The potential pathogenetic role of GSS-ß 1-mediated Na+-K+ pump dysfunction in preeclampsia was investigated. RESULTS: Protein expression of the ß 1 subunit was unchanged in placentas from women with preeclampsia vs those with normotensive pregnancies. Preeclamptic placentas had a significantly increased GSS-ß 1 of the Na+-K+ pump compared to those from healthy pregnancies, and this was linked to a decrease in α 1/ß 1 subunit coimmunoprecipitation. The cytosolic p47phox nicotinamide adenine dinucleotide phosphate hydrogen (NADPH) oxidase subunit and its coimmunoprecipitation with the α 1 Na+-K+ pump subunit was increased in preeclamptic placentas, thus implicating NADPH oxidase-dependent pump inhibition. CONCLUSIONS: The high level of ß 1 pump subunit glutathionylation provides new insights into the mechanism of Na+-K+ pump dysfunction in preeclampsia.

Accuracy of hiatal hernia diagnosis in bariatric patients: Preoperative endoscopy versus intraoperative reference.

BACKGROUND AND AIM: Obesity is becoming increasingly prevalent in Asia. Bariatric surgery in the region is growing in popularity to reflect increasing demand. Hiatal hernia (HH) is common among the obese population. There is a lack of evidence comparing preoperative endoscopy against intraoperative findings as a standard of reference for HH diagnosis. METHODS: This was a retrospective analysis of a bariatric procedure database from a single tertiary teaching hospital and high-volume endoscopy center. Electronic medical records were reviewed. Endoscopy results were compared to intraoperative findings, and subgroup analysis of >2 cm hernias was performed. Sensitivity, specificity, predictive values, likelihood ratios, and global diagnostic test accuracy were calculated. RESULTS: A total of 434 patients were eligible for this study, of which HH was detected in 37 patients (prevalence rate 8.55%). Mean age was 41.51 ± 11.07 years, and body mass index was 39.37 ± 5.67 kg/m2. Endoscopy sensitivity was 75.68% (95% confidence interval, 58.80-88.23%) and specificity 91.44% (88.24-94.00%). Positive likelihood ratio was 8.53 (6.11-12.79) and negative likelihood ratio 0.27 (0.15-0.47). Positive predictive value was 45.16% (36.27-54.38%) and negative predictive value 97.58% (95.80-98.62%). Accuracy of endoscopy for preoperative HH diagnosis was 90.09% (86.89-92.74%). CONCLUSION: Endoscopy can have a high diagnostic accuracy of preoperative HH diagnosis in obese Asian patients using intraoperative diagnosis as the reference standard.

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.