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.

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.

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.

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.

Adolescent Perinatal Outcomes in South West Sydney, Australia.

OBJECTIVE: To compare perinatal outcomes, blood pressures throughout pregnancy, rates of hypertensive disorders of pregnancy, preeclampsia, gestational diabetes mellitus, and immediate obstetric outcomes in adolescents younger than 20 years at delivery and those in the 20- to 34-year age group. PATIENTS AND METHODS: Questionnaires were administered to pregnant women at Campbelltown and Liverpool hospitals within South West Sydney, Australia, as part of a broader study of sleep-disordered breathing in pregnancy between February 1, 2009, and February 28, 2013. Data collected included demographic data, blood pressure readings, pregnancy complications, delivery type, and neonatal outcomes. Adolescents were compared with older women using Student t tests and χ2 statistics. RESULTS: A total of 103 adolescents were compared with 2291 women aged 20 to 34 years. Adolescents were more likely to be primiparous, had longer average gestations, and had lower pre-pregnancy body mass index. Adolescents had lower rates of cesarean section delivery and gestational diabetes mellitus. There was no significant difference in smoking rates, perinatal mortality rate, small for gestational age, intrauterine growth restriction, Apgar score of less than 7 at 5 minutes, admission to special care nursery, or hypertensive disorder of pregnancy rates. Adolescents had lower booking systolic and diastolic blood pressures, and their highest antenatal systolic blood pressures were lower. CONCLUSION: Adolescents have birth outcomes to similar to those of their older counterparts. Adolescents had lower booking blood pressures. This may have implications for the screening and diagnosis of hypertensive disorders of pregnancy in adolescents.