Magnetic resonance imaging and cerebrovascular hemodynamics in (pre)-eclampsia

Hoge bloeddruk tijdens de zwangerschap is gevaarlijk. De mogelijke gevolgen, zoals hersenoedeem, stuipen en hersenbloedingen, eisen jaarlijks wereldwijd 50 tot 65 duizend vrouwenlevens. Ook in Nederland is deze zogeheten 'preëclampsie' de hoofdoorzaak van moedersterfte. Toch grijpen artsen vaak te laat in volgens Gerda Zeeman. Dit omdat er te weinig bekend is in de medische wetenschap over veranderingen in de hersendoorbloeding. Ook leren de handboeken dat vrouwen in principe geheel herstellen. Zeeman bracht als eerste de veranderingen in de hersenen in beeld en constateert onder meer dat er wel degelijk blijvende schade kan zijn. Hoge bloeddruk komt ongeveer bij vijf tot tien procent van de zwangerschappen voor. Bij een patiënt met preëclampsie (ook wel zwangerschapsvergiftiging of toxicose genoemd) kunnen stuipen ontstaan, soms gevolgd door een hersenbloeding. Dit komt omdat de bloeddruk dan acuut stijgt. Zeeman heeft tijdens haar opleiding veel ervaring opgedaan met de behandeling van deze patiënten: ‘Een stuipende vrouw zorgt voor een angstaanjagend moment voor artsen en verpleegkundigen en het is een drama wanneer je een moeder daarna ziet overlijden.’ Medische handboeken onderwijzen dat een vrouw geheel herstelt na stuipen en dat hersenbloedingen zeldzaam zijn. Daarom wordt er momenteel vaak veel te laat gestart met bloeddrukverlagende medicatie. Maar een groot deel van de vrouwen lijkt jarenlang verschijnselen over te houden aan de stuipen, zoals geheugenverlies en gebrek aan concentratievermogen. Blijvende schade Het is bekend dat zwangerschap voor grote veranderingen zorgt in de belasting van hart en bloedvaten, maar de veranderingen in de doorbloeding van de hersenen zijn tot nu toe nagenoeg niet onderzocht. Daarom zijn artsen onzeker welke preventie of behandeling toe te passen. Met moderne MRI-technieken bracht Zeeman in beeld dat bij gezonde zwangere vrouwen de bloeddoorstroming in de hersenen afneemt, terwijl er juist een toename is bij vrouwen met zwangerschapshypertensie. Waarschijnlijk leidt dit mechanisme uiteindelijk tot stuipen. Verder ontdekte de promovendus dat een kwart van de patiënten in meer of mindere mate blijvende hersenschade overhoudt aan stuipen. Stuipen en hersenbloedingen zijn in veel gevallen te voorkomen door tijdig de bloeddruk te verlagen en magnesiumsulfaat toe te dienen. Dat gebeurt helaas nog veel te weinig in Nederland. Hoe het magnesiumsulfaat werkt is niet bekend. Men denkt dat het samentrekking van de hersenvaten tegengaat, maar Zeeman ontdekte dat het gunstige effect van magnesiumsulfaat daar niet aan toe te schrijven is

Magnetic resonance imaging and cerebrovascular hemodynamics in (pre)-eclampsia

Hoge bloeddruk tijdens de zwangerschap is gevaarlijk. De mogelijke gevolgen, zoals hersenoedeem, stuipen en hersenbloedingen, eisen jaarlijks wereldwijd 50 tot 65 duizend vrouwenlevens. Ook in Nederland is deze zogeheten 'preëclampsie' de hoofdoorzaak van moedersterfte. Toch grijpen artsen vaak te laat in volgens Gerda Zeeman. Dit omdat er te weinig bekend is in de medische wetenschap over veranderingen in de hersendoorbloeding. Ook leren de handboeken dat vrouwen in principe geheel herstellen. Zeeman bracht als eerste de veranderingen in de hersenen in beeld en constateert onder meer dat er wel degelijk blijvende schade kan zijn. Hoge bloeddruk komt ongeveer bij vijf tot tien procent van de zwangerschappen voor. Bij een patiënt met preëclampsie (ook wel zwangerschapsvergiftiging of toxicose genoemd) kunnen stuipen ontstaan, soms gevolgd door een hersenbloeding. Dit komt omdat de bloeddruk dan acuut stijgt. Zeeman heeft tijdens haar opleiding veel ervaring opgedaan met de behandeling van deze patiënten: ‘Een stuipende vrouw zorgt voor een angstaanjagend moment voor artsen en verpleegkundigen en het is een drama wanneer je een moeder daarna ziet overlijden.’ Medische handboeken onderwijzen dat een vrouw geheel herstelt na stuipen en dat hersenbloedingen zeldzaam zijn. Daarom wordt er momenteel vaak veel te laat gestart met bloeddrukverlagende medicatie. Maar een groot deel van de vrouwen lijkt jarenlang verschijnselen over te houden aan de stuipen, zoals geheugenverlies en gebrek aan concentratievermogen. Blijvende schade Het is bekend dat zwangerschap voor grote veranderingen zorgt in de belasting van hart en bloedvaten, maar de veranderingen in de doorbloeding van de hersenen zijn tot nu toe nagenoeg niet onderzocht. Daarom zijn artsen onzeker welke preventie of behandeling toe te passen. Met moderne MRI-technieken bracht Zeeman in beeld dat bij gezonde zwangere vrouwen de bloeddoorstroming in de hersenen afneemt, terwijl er juist een toename is bij vrouwen met zwangerschapshypertensie. Waarschijnlijk leidt dit mechanisme uiteindelijk tot stuipen. Verder ontdekte de promovendus dat een kwart van de patiënten in meer of mindere mate blijvende hersenschade overhoudt aan stuipen. Stuipen en hersenbloedingen zijn in veel gevallen te voorkomen door tijdig de bloeddruk te verlagen en magnesiumsulfaat toe te dienen. Dat gebeurt helaas nog veel te weinig in Nederland. Hoe het magnesiumsulfaat werkt is niet bekend. Men denkt dat het samentrekking van de hersenvaten tegengaat, maar Zeeman ontdekte dat het gunstige effect van magnesiumsulfaat daar niet aan toe te schrijven is.

Neurocognitive functioning following preeclampsia and eclampsia:a long-term follow-up study

ObjectiveWomen who suffered preeclampsia and eclampsia may report subjective cognitive difficulties in daily life, the interpretation of which is cumbersome, because these are affected by emotional factors. Previous studies only included preeclamptic women investigated shortly after pregnancy. We aimed to determine whether these subjective reports of cognitive difficulty could be interpreted as reflecting objective cognitive dysfunction. Therefore, cognitive functioning was assessed using standardized neurocognitive tests in both preeclamptic and eclamptic women several years following the index pregnancy.Study DesignForty-six formerly eclamptic, 51 formerly preeclamptic, and 48 control women who had normotensive pregnancies, age-matched, participated in this study. Average elapsed time since index pregnancy was 7 years. Neurocognitive tests were divided into 6 domains; visual perception, motor functions, working memory, long-term memory, attention, and executive functioning. Subjective cognitive functioning was measured by the Cognitive Failures Questionnaire and anxiety/depression by the Hospital Anxiety and Depression Scale.ResultsBoth preeclamptic and eclamptic women performed worse on the motor functions domain (P < .05), without differences on the other domains. They scored worse on the Cognitive Failures Questionnaire (P < .01), the Hospital Anxiety and Depression Scale anxiety (P < .01), and depression (P < .05) subscales.ConclusionWomen who suffered eclampsia and/or preeclampsia demonstrate no objective cognitive impairment as compared with controls. Contrary to the well-structured test setting, both groups do report more cognitive failures, which are thought to reflect neurocognitive dysfunction in complex, stressful daily-life situations. Such report of cognitive failures may be compounded by anxiety and depression. Future studies should focus on the relationship of neurocognitive functioning with structural cerebral abnormalities

Cerebral white matter lesions and perceived cognitive dysfunction: the role of pregnancy

ObjectiveWomen who suffered eclampsia or preterm preeclampsia are twice as likely to demonstrate cerebral white matter lesions (WML) on magnetic resonance imaging compared with age-matched women who had normotensive pregnancies, and they report more cognitive dysfunctions in everyday life. We aimed to determine whether pregnancy in and of itself has a relationship with the presence of WML and subjective cognitive dysfunction.Study DesignEighty-one parous women who had a normotensive pregnancy were matched for age with 65 nulliparous women and all underwent cerebral magnetic resonance imaging. Presence of cerebral WML was rated and blood pressure was measured. Subjective cognitive functioning was assessed using the Cognitive Failures Questionnaire.ResultsThere was no difference in the presence (22% vs 19%) of WML between parous and nulliparous women. Age was a predictor for the presence of WML, whereas the presence of current hypertension was not. Average score on the Cognitive Failures Questionnaire was not different between both groups, nor related to WML.ConclusionA history of pregnancy in and of itself is not related to the presence of cerebral WML and the perception of cognitive dysfunction. Because of the relationship with preterm preeclampsia and eclampsia, future research should focus on the clinical importance and development throughout the years of such cerebral WML in young women and focus on risk factors for cardiovascular disease

Cerebral white matter lesions, subjective cognitive failures, and objective neurocognitive functioning:A follow-up study in women after hypertensive disorders of pregnancy

OBJECTIVE: Hypertensive disorders of pregnancy, like preeclampsia, are a leading cause of maternal and fetal morbidity/mortality worldwide. Preeclampsia can be complicated by the occurrence of convulsions (eclampsia). Women who experienced (pre)eclampsia more frequently report daily cognitive failures and showed increased emotional dysfunction several years later, but are not impaired on objective neurocognitive testing. In addition, women with preterm preeclampsia more often have cerebral white matter lesions (WML) on follow-up. We aimed to determine whether WML presence is related to cognitive dysfunction, anxiety, and depressive symptoms in (pre)eclamptic women. METHOD: Forty-one eclamptic, 49 preeclamptic, and 47 control women who had a normotensive pregnancy completed the Cognitive Failures Questionnaire (CFQ), the Hospital Anxiety and Depression Scale (HADS), and a broad neurocognitive test battery (visual perception and speed of information processing, motor functions, working memory, long-term memory, attention, and executive functioning). All underwent cerebral magnetic resonance imaging (MRI), and WML presence was recorded. Median elapsed time since index pregnancy was 6 years. Average age was 40 years. RESULTS: WML were more prevalent in women who had experienced preterm (pre)eclampsia (<37 weeks; 40%) than in controls (21%, p = .03). In (pre)eclamptic women, CFQ and HADS scores were higher than those in controls (44± 16.1 vs. 36± 11.0, p < .001, and 11± 6.3 vs. 8± 5.5, p < .001). There was no difference in objective cognitive performance as measured by neurocognitive tests. Subjective and objective cognitive functioning, anxiety, and depressive symptoms were not related to WML presence. CONCLUSION: Formerly (pre)eclamptic women report cognitive dysfunction, but do not exhibit overt cognitive impairment when objectively tested on average 6 years following their pregnancy. The presence of WML is not related to objective nor to subjective cognitive impairment, anxiety, and depressive symptoms. Longitudinal studies are needed to study whether the presence of WML is a risk factor for developing objective cognitive impairment in the long term

Duration of second victim symptoms in the aftermath of a patient safety incident and association with the level of patient harm: A cross-sectional study in the Netherlands

OBJECTIVES: To describe healthcare providers' symptoms evoked by patient safety incidents (PSIs), the duration of these symptoms and the association with the degree of patient harm caused by the incident. DESIGN: Cross-sectional survey. SETTING: 32 Dutch hospitals that participate in the 'Peer Support Collaborative'. PARTICIPANTS: 4369 healthcare providers (1619 doctors and 2750 nurses) involved in a PSI at any time during their career. INTERVENTIONS: All doctors and nurses working in direct patient care in the 32 participating hospitals were invited via email to participate in an online survey. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of symptoms, symptom duration and its relationship with the degree of patient harm. RESULTS: In total 4369 respondents were involved in a PSI and completely filled in the questionnaire. Of these, 462 reported having been involved in a PSI with permanent harm or death during the last 6 months. This had a personal, professional impact as well as impact on effective teamwork requirements. The impact of a PSI increased when the degree of patient harm was more severe. The most common symptom was hypervigilance (53.0%). The three most common symptoms related to teamwork were having doubts about knowledge and skill (27.0%), feeling unable to provide quality care (15.6%) and feeling uncomfortable within the team (15.5%). PSI with permanent harm or death was related to eightfold higher likelihood of provider-related symptoms lasting for more than 1\u2009month and ninefold lasting longer than 6\u2009months compared with symptoms reported when the PSI caused no harm. CONCLUSION: The impact of PSI remains an underestimated problem. The higher the degree of harm, the longer the symptoms last. Future studies should evaluate how these data can be integrated in evidence-based support systems

Long-Term Visual Functioning After Eclampsia

OBJECTIVE: Complete neurocognitive recovery after eclampsia has been questioned with the expression of neurocognitive deficits by affected women and demonstration of cerebral white matter lesions on magnetic resonance imaging years after eclampsia. We hypothesized that formerly eclamptic women may experience impaired vision-related quality of life (QOL) and visual field loss as a result of the presence of such lesions in the cerebral visual areas. METHODS: Using the National Eye Institute Visual Function Questionnaire-39/Nederlands questionnaire, vision-related QOL was compared between formerly eclamptic women and control participants after normotensive pregnancies. Furthermore, in formerly eclamptic women, visual fields were assessed using automated perimetry, and presence of white matter lesions was evaluated using cerebral magnetic resonance imaging. Presence of a relationship between these lesions and National Eye Institute Visual Function Questionnaire-39/Nederlands scores was estimated. RESULTS: Forty-seven formerly eclamptic women and 47 control participants participated 10.1 +/- 5.2 and 11.5 +/- 7.8 years after their index pregnancy, respectively. Composite scores and 4 out of 12 National Eye Institute Visual Function Questionnaire-39/Nederlands subscale scores were significantly lower in formerly eclamptic women than in control participants (P CONCLUSION: Formerly eclamptic women express lower vision-related QOL than control participants, which seemed at least partly related to the presence of white matter lesions. However, such women do not have unconscious visual field loss. Vision-related QOL impairment expressed by formerly eclamptic women may therefore be related to problems with higher-order visual functions

Induction of Labor for Maternal Indications at a Periviable Gestational Age; Survey on Management, Reporting and Auditing amongst Dutch Maternal-Feta Medicine Specialists and Neonatologists

Background In cases of life-threatening maternal conditions in the periviable period, professionals may consider immediate delivery with fetal demise as a consequence of the treatment. We sought the opinion of involved medical professionals on management, reporting, and auditing in these cases.Methods We performed an online survey amongst all registered maternal-fetal medicine (MFM) specialists and neonatologists in the Netherlands. The survey presented two hypothetical cases of severe early-onset pre-eclampsia at periviable gestational ages. Management consisted of immediate termination or expectant management directed towards newborn survival.Findings In the case managed by immediate termination, 62% percent answered that fetal demise resulting from induction of labor for maternal indications should be audited only within the medical profession. In the case of expectant management, 17% of the participants agreed with this management. Some answers revealed a significant difference in opinion between the medical specialists.Conclusion Perspective of MFM specialists and neonatologists differs with regard to counseling prospect parents in case of severe early onset pre-eclampsia. The majority of professionals is willing to report late termination (after 24 weeks' gestation) for severe maternal disease to medical experts for internal audits but not for legal auditing.</p

A multi-centre phase IIa clinical study of predictive testing for preeclampsia: Improved pregnancy outcomes via early detection (IMPROvED)

Background: 5% of first time pregnancies are complicated by pre-eclampsia, the leading cause of maternal death in Europe. No clinically useful screening test exists; consequentially clinicians are unable to offer targeted surveillance or preventative strategies. IMPROvED Consortium members have pioneered a personalised medicine approach to identifying blood-borne biomarkers through recent technological advancements, involving mapping of the blood metabolome and proteome. The key objective is to develop a sensitive, specific, high-throughput and economically viable early pregnancy screening test for pre-eclampsia.Methods/Design: We report the design of a multicentre, phase IIa clinical study aiming to recruit 5000 low risk primiparous women to assess and refine innovative prototype tests based on emerging metabolomic and proteomic technologies. Participation involves maternal phlebotomy at 15 and 20 weeks' gestation, with optional testing and biobanking at 11 and 34 weeks. Blood samples will be analysed using two innovative, proprietary prototype platforms; one metabolomic based and one proteomic based, both of which outperform current biomarker based screening tests at comparable gestations. Analytical and clinical data will be collated and analysed via the Copenhagen Trials Unit.Discussion: The IMPROvED study is expected to refine proteomic and metabolomic panels, combined with clinical parameters, and evaluate clinical applicability as an early pregnancy predictive test for pre-eclampsia. If 'at risk' patients can be identified, this will allow stratified care with personalised fetal and maternal surveillance, early diagnosis, timely intervention, and significant health economic savings. The IMPROvED biobank will be accessible to the European scientific community for high quality research into the cause and prevention of adverse pregnancy outcome.Trial registration: Trial registration number NCT01891240. The IMPROvED project is funded by the seventh framework programme for Research and Technological development of the EU. http://www.fp7-improved.eu/