Use of the USCOM® noninvasive cardiac output measurement system to predict the development of pre-eclampsia in hypertensive pregnancies.

OBJECTIVES: To assess the ability of the USCOM® (USCOM), using measurements of cardiac output (CO) and systemic vascular resistance (SVR), to predict the development of pre-eclampsia (PE) and severe PE in hypertensive pregnancies. STUDY DESIGN: Prospective cohort study of women in the second or third trimester recruited at a tertiary center in Sydney, Australia. Demographic data and hemodynamic measurements using the USCOM were taken for all study participants at recruitment. Pregnancy outcome, including development of PE and severe PE, was tracked. Data were analyzed using ANOVA testing, pair-wise comparison testing, and Student's t-testing. RESULTS: Recruitment included 65 normotensive controls, 34 women with chronic hypertension (CH), 51 with gestational hypertension (GH), and 21 with PE. Significantly higher weight, body surface area, and blood pressure measurements were found in the hypertensive, compared with the normotensive control and pregnancies. There were no observed differences in USCOM-measured CO, cardiac index, SVR, or systemic vascular resistance index between hypertensive women who did versus did not develop PE or severe PE in later pregnancy. Analysis of the CH and GH subgroups, as well as only unmedicated hypertensive women (n = 24), also showed no significant difference in hemodynamic parameters between those who did or did not develop PE or severe PE. CONCLUSIONS: Our group was unable to successfully predict the onset of PE or severe PE based on hemodynamic parameters measured with the USCOM. It is possible this relates to the high proportion of women on antihypertensive medication at recruitment.

Preeclampsia-Associated Cardiovascular Risk Factors 6 Months and 2 Years After Pregnancy: The P4 Study.

BACKGROUND: Increased cardiovascular risk following preeclampsia is well established and there are signs of early cardiovascular aging 6 months postpartum. This study assessed whether blood pressure (BP) and other cardiovascular measures are abnormal 2 years postpartum in the same cohort to determine ongoing risk markers. METHODS: Six months and 2 years postpartum, BP was measured using sphygmomanometry, 24-hour ambulatory BP monitoring, and noninvasive central BP. Anthropometric measures, blood, and urine biochemistry were performed. Cross-sectional comparisons between preeclampsia and normotensive pregnancy (NP) groups and longitudinal comparisons within each group were made at 6 months and 2 years. RESULTS: Two years postpartum, 129 NP, and 52 preeclampsia women were studied who also had 6 months measures. At both time points, preeclampsia group had significantly higher BP (office BP 2 years, 112±12/72±8 versus 104±9/67±7 mm Hg NP; [P<0.001]; mean ambulatory BP monitoring 116±9/73±8 versus 106±8/67±6 mm Hg NP; [P<0.001]). No significant BP changes noted 6 months to 2 years within either group. Office BP thresholds of 140 mm Hg systolic and 90 mm Hg diastolic classified 2% preeclampsia and 0% NP at 2 years. American Heart Association 2017 criteria (above normal, >120/80 mm Hg) classified 25% versus 8% (P<0.002), as did our reference range threshold of 122/79 mm Hg. American Heart Association criteria classified 60% post-preeclampsia versus 16% after NP with above-normal ambulatory BP monitoring (P<0.001). Other cardiovascular risk markers more common 2 years post-preeclampsia included higher body mass index (median 26.6 versus 23.1, P=0.003) and insulin resistance. CONCLUSIONS: After preeclampsia, women have significantly higher BP 6 months and 2 years postpartum, and have higher body mass index and insulin-resistance scores, increasing their future cardiovascular risk. Regular cardiovascular risk screening should be implemented for all who have experienced preeclampsia.

Growth from birth to 6 months of infants with and without intrauterine preeclampsia exposure.

Intrauterine preeclampsia exposure affects the lifelong cardiometabolic health of the child. Our study aimed to compare the growth (from birth to 6 months) of infants exposed to either a normotensive pregnancy or preeclampsia and explore the influence of being born small for gestational age (SGA). Participants were children of women participating in the Post-partum, Physiology, Psychology and Paediatric follow-up cohort study. Birth and 6-month weight and length z-scores were calculated for term and preterm (<37 weeks) babies, and change in weight z-score, rapid weight gain (≥0.67 increase in weight z-score) and conditional weight gain z-score were calculated. Compared with normotensive exposed infants (n = 298), preeclampsia exposed infants (n = 84) were more likely to be born SGA (7% versus 23%; P < 0.001), but weight gain from birth to 6 months, by any measure, did not differ between groups. Infants born SGA, irrespective of pregnancy exposure, were more likely to have rapid weight gain and had greater increases in weight z-score compared with those not born SGA. Preeclampsia exposed infants born SGA may benefit from interventions designed to prevent future cardiometabolic disease.

Maternal Adiposity and Energy Balance After Normotensive and Preeclamptic Pregnancies.

BACKGROUND: Preeclampsia is a major pregnancy complication associated with long-term maternal cardiometabolic disease. Research generally is focused on metabolic and pathophysiological changes during pregnancy; however, there is much less focus on the early postpartum period in subjects who suffered preeclampsia. The aim of this study was to (1) characterize energy intake and expenditure 6 months following normotensive and preeclamptic pregnancies and (2) examine associations between energy balance, body composition, insulin resistance measures (HOMA-IR), and clinical characteristics. DESIGN: A cross-sectional study 6 months following normotensive (n = 75) and preeclamptic (n = 22) pregnancies was performed. Metabolic measurements included anthropometrics measures, body composition via bioelectrical impedance analysis, 24-h energy expenditure via SenseWear Armbands, energy intake via a 3-day food diary, and serum metabolic parameters. RESULTS: Six months following preeclampsia, women had a significantly higher weight (77.3 ± 20.9 kg vs 64.5 ± 11.4 kg, P = 0.01), fat mass percentage (FM%; 40.7 ± 7.4% vs 34.9 ± 8.1%, P = 0.004), and insulin resistance (HOMA-IR 2.2 ± 1.5 vs 1.0 ± 0.7, P = 0.003), as well as reduced HDL levels (1.5 ± 0.4 mmol/L vs 1.8 ± 0.4 mmol/L, P = 0.01) compared to normotensive women. Women post-preeclampsia had lower activity-related energy expenditure (P = 0.02) but a decreased total energy intake (P = 0.02), leading to a more negative energy balance compared to their normotensive counterparts (-1942 kJ/24 h vs -480 kJ/24 h, P = 0.02). CONCLUSION: Increases in insulin resistance and FM%, reduced high-density lipoprotein, and more sedentary lifestyles characterize the postpartum period following preeclamptic compared with normotensive pregnancies. Early post-preeclampsia interventions, such as lifestyle behavior change, should be implemented and assessed to determine whether they reduce long-term cardiometabolic risk in women who experienced preeclampsia during pregnancy.

Recognizing Cardiovascular Risk After Preeclampsia: The P4 Study.

Background There is increased risk of hypertension, early cardiovascular disease, and premature mortality in women who have had preeclampsia. This study was undertaken to determine the upper limit of normal blood pressure (BP) 6 months postpartum and the frequency of women with prior preeclampsia who had BP above these limits, as part of the P4 (Post-Partum Physiology, Psychology and Pediatric) follow-up study. Methods and Results BP was measured by sphygmomanometer, 24-hour ambulatory BP monitoring, and non-invasive central BP at 6 months postpartum in 302 women who had normotensive pregnancy and 90 who had preeclampsia. The upper limit of normal BP (mean+2 SD) for women with normotensive pregnancy was 122/79 mm Hg for routine BP, 115/81 mm Hg for central BP, and 121/78 mm Hg for 24-hour ambulatory BP monitoring. Traditional normal values detected only 3% of women who had preeclampsia as having high BP 6 months postpartum whereas these new values detected between 13% and 19%. Women with preeclampsia had greater body mass index (27.8 versus 25.0, P<0.001) and left ventricular wall thickness but similar augmentation index. They also had lower high-density lipoprotein (59±15 versus 65±16 mg/dL, P=0.002), higher triglycerides (77±51 versus 61±35 mg/dL, P=0.005), and higher homeostatic model assessment score (2.1±1.8 versus 1.3±1.9, P<0.001). Conclusions Clinicians wishing to detect high BP in these women should be aware of the lower than usual upper limit of normal for this young cohort and where possible should use 24-hour ambulatory BP monitoring to detect these changes. This may define a subgroup of women who had preeclampsia for whom targeted BP lowering therapy would be successful. Registration URL: https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365295&isReview=true; Unique identifier: ACTRN12613001260718.

Blood pressure postpartum (BP2) RCT protocol: Follow-up and lifestyle behaviour change strategies in the first 12 months after hypertensive pregnancy.

OBJECTIVES: Women who had hypertensive disorders of pregnancy (HDP) are twice as likely to experience maternal cardiovascular disease later in life. The primary aim of this study (BP2) is to compare outcomes of 3 different management strategies, including lifestyle behaviour change (LBC), in the first 12 months postpartum in women who had HDP in their preceding pregnancy. Secondary aims include assessing the effects on other cardiometabolic parameters. STUDY DESIGN: Three-arm multicentre randomised trial in metropolitan Australian hospitals, (registration: ACTRN12618002004246) target sample size 480. Participants are randomised to one of three groups: 1) Optimised usual care: information package and family doctor follow-up 6 months postpartum 2) Brief intervention: information package as per group 1, plus assessment and brief LBC counselling at a specialised clinic with an obstetric physician and dietitian 6 months postpartum 3) Extended intervention: as per group 2 plus enrolment into a 6 month telephone-based LBC program from 6 to 12 months postpartum. All women have an outcome assessment at 12 months. MAIN OUTCOME MEASURES: Primary outcomes: (a) BP change or (b) weight change and/or waist circumference change. SECONDARY OUTCOMES: maternal health-related quality of life, engagement and retention in LBC program, biochemical markers, vascular function testing, infant weight trajectory, incremental cost-effectiveness ratios. The study is powered to detect a 4 mmHg difference in systolic BP between groups, or a 4 kg weight loss difference/2cm waist circumference change. CONCLUSIONS: BP2 will provide evidence regarding the feasibility and effectiveness of postpartum LBC interventions and structured clinical follow-up in improving cardiovascular health markers after HDP.

Crystalglobulinemia in Multiple Myeloma: A Rare Case Report of Survival and Renal Recovery.

RATIONALE: Crystalglobulinemia is a rare complication of monoclonal gammopathy wherein crystallized immunoglobulins deposit in various organs causing occlusive vasculopathy, endothelial damage, and thrombosis. It should be differentiated from light chain cast nephropathy without crystalline nephropathy through timely diagnosis with a kidney biopsy. PRESENTING CONCERNS OF THE PATIENT: We report a case of a 74-year-old female with polyarthralgia, chest pain, petechial rash, and acute kidney injury. DIAGNOSES: Kidney biopsy revealed eosinophilic casts in the tubular lumen and similar occlusive crystalline deposits within the glomerular vasculature and interlobular arteries. Bone marrow biopsy and serum electrophoresis confirmed immunoglobulin G (IgG) κ multiple myeloma. INTERVENTIONS: Dialysis was initiated for severe oligoanuric acute kidney injury. The patient was treated with 5 sessions of plasmapheresis and 11 cycles of clone reduction chemotherapy with CyBorD (cyclophosphamide, bortezomib, and dexamethasone). OUTCOMES: This patient achieved excellent kidney recovery and is no longer dialysis dependent. TEACHING POINTS: Crystalglobulinemia should be suspected in patients with rapidly progressive acute kidney injury and monoclonal gammopathy. Timely investigation with kidney biopsy to differentiate this condition from light chain cast nephropathy and initiation of appropriate treatment can lead to remission of disease and excellent recovery of kidney function.

JUSTIFICATION: La cristalglobulémie, une complication rare de la gammapathie monoclonale, se caractérise par la présence de dépôts d'immunoglobulines cristallisées dans différents organes, ce qui entraîne une vasculopathie occlusive, des lésions endothéliales et une thrombose. Un diagnostic précoce par biopsie rénale doit être posé pour différencier la cristalglobulinémie de la néphropathie en chaînes légères sans néphropathie cristalline. PRÉSENTATION DU CAS: Nous présentons le cas d'une patiente de 74 ans souffrant de polyarthralgie, de douleurs thoraciques, d'une éruption pétéchiale et d'insuffisance rénale aiguë. DIAGNOSTIC: La biopsie rénale a révélé la présence de cylindres éosinophiles dans la lumière tubulaire et de dépôts cristallins occlusifs similaires dans le système vasculaire des glomérules et dans les artères interlobulaires. La biopsie de la moelle osseuse et l'électrophorèse sérique ont confirmé la présence d'un myélome multiple à immunoglobulines G (IgG) κ. INTERVENTIONS: L'insuffisance rénale aiguë oligoanurique grave a nécessité l'amorce d'une dialyse. Le traitement a consisté en cinq séances de plasmaphérèse et onze 11 cycles de chimiothérapie de réduction des clones avec CyBorD (cyclophosphamide, bortézomib et dexaméthasone). RÉSULTATS: Le rétablissement rénal est excellent et la patiente n'est plus sous dialyse. LEÇONS TIRÉES: Une cristalglobulinémie doit être suspectée chez les patients qui présentent une gammapathie monoclonale et une insuffisance rénale aigüe rapidement progressive. Le diagnostic rapide par biopsie rénale pour différencier cette affection d'une néphropathie à chaînes légères et l'initiation précoce du traitement approprié peut mener à une rémission et à une excellente récupération de la fonction rénale.

Postpartum physiology, psychology and paediatric follow up study (P4 Study) - Study protocol.

BACKGROUND: Women who have had hypertension in pregnancy are at greater risk of long term cardiovascular disease (CVD). Little is known about their cardiovascular risk postpartum or the effects on the woman's mental health and the outcomes of their infants. In this project we will study the physiological and psychological health of women and the physical health and development of their infants six months, two years and five years after birth. We will establish normal blood pressure (BP) and metabolic function for women who were normotensive in pregnancy and use these to assess women who had gestational hypertension (GH) or preeclampsia (PE). DESIGN/METHODS: Women will be asked to participate if they have given birth in the preceding six months. They will be excluded if they had diabetes, hypertension, renal or other serious maternal disease prior to pregnancy or congenital anomaly in the pregnancy. We will recruit 292 women who were normotensive and their babies, 100 who had GH and 100 who had PE and their babies. They will be assessed at six months, two and five years after birth. At each assessment mothers will have their blood pressure (BP) assessed peripherally with a liquid crystal sphygmomanometer and 24h ambulatory blood pressure monitoring (ABPM), and centrally with non-invasive applanation tonometry. Additional physiological testing will include: body composition; energy balance; vascular compliance; cardiac function; liver and renal function, lipids and biochemistry; glucose and insulin; and urinalysis. Psychological status will be assessed with validated self-report questionnaires for depression, anxiety, post-traumatic stress disorder (PTSD) and mother-infant bonding. The babies will have a medical examination by a paediatrician at each assessment. Their behavioural development will be assessed with an Ages and Stages Questionnaire completed by their mother at each assessment and a developmental assessment by a child psychologist at two and five years. CONCLUSIONS: This study will re-define normal BP and other physiological parameters for young parous women thereby permitting a more sensitive assessment of post-partum BP and other cardiovascular risk markers in women who have had GH or PE. It will also determine the extent, if any, of psychological disorders in these women and developmental or other concerns in their babies. TRIALS REGISTRATION: Australian and New Zealand Clinical Trials Registry Number: ACTRN12613001260718.

All that wheezes is not asthma: A cautionary case study of shortness of breath in pregnancy.

BACKGROUND: Shortness of breath is a common physiological pregnancy presentation, secondary to both hormonal and mechanical effects. Its pathological causes are common (asthma exacerbation or infection); new-onset cardiac pathology is rarely considered. CASE: JC, a 39-year old G4P2T1, presented at 34 weeks' gestation with shortness of breath unrelieved by salbutamol. History included asthma, poly-drug abuse and smoking. Initial presentation was consistent with asthma exacerbation and she was treated as such. There was deterioration of symptoms and on re-examination raised jugular venous pressure was noted with bibasal lung crepitations and cardiac systolic murmur. Echocardiogram showed severe cardiomyopathy (left ventricular ejection fraction 20%). JC was commenced on diuretics, digoxin and fluid restricted. Labour was induced at 35 weeks' gestation, with birth of a healthy female infant (BW 2475 g) by elective assisted vaginal delivery. Cardiac function improved in subsequent weeks, confirming peripartum cardiomyopathy. CONCLUSION: Peripartum cardiomyopathy affects 1 in 2500-4000 live births. Over 90% of women regain normal cardiac function postpartum with optimal medical management. Peripartum cardiomyopathy presents a diagnostic conundrum as its primary symptoms mimic not only those of normal pregnancy but also a number of other, more common conditions. It is important to consider cardiac causes of shortness of breath initially, and vital to revisit an initial non-cardiac shortness of breath diagnosis if there is no sustained improvement with treatment. In this case, asthma history and initial wheeze on examination impeded correct diagnosis; however, the situation was re-evaluated and correct diagnosis made when the patient's shortness of breath deteriorated. Subsequent multidisciplinary management and birth in an appropriate setting facilitated the best outcome for both mother and baby.

The management of pre-eclampsia: what we think we know.

The focus of this article is to review and challenge some current concepts surrounding the diagnosis and management of pre-eclampsia as well as considering where our management might head in the future. Pre-eclampsia is a syndrome defined by the new onset of hypertension in the 2nd half of pregnancy that is generally, but not always, accompanied by proteinuria. Whilst in recent times our understanding and management of this condition have improved there are some areas where evidence and opinions differ. In this review we will discuss the diagnosis of pre-eclampsia and the concept of the 'atypical' presentation. We will outline how to identify those women with pre-eclampsia who will have a poorer pregnancy outcome. We will address the question of when to deliver and how to treat if we decide to prolong the pregnancy. Finally we acknowledge that pre-eclampsia is more than a disorder of pregnancy and has lifelong implications for the mother and infant.