Subsequent pregnancy outcome after mid-trimester termination of pregnancy for preeclampsia.

BACKGROUND: In this study we determined the outcome of subsequent pregnancies after termination of pregnancy for preeclampsia, with the purpose of presenting data useful for counselling these women on future pregnancies. STUDY DESIGN: The cohort consisted of 131 women with a history of termination of pregnancy for preeclampsia. RESULTS: Data of 79 pregnancies were available for analysis, including 13 women with chronic hypertension and 16 women with thrombophilia. There were seven miscarriages (8.8%) and 72 ongoing pregnancies. Low-dose aspirin was prescribed for 64 women (89%). The mean gestational age at delivery was 356/7 ± 4 weeks with a mean birth weight of 2571 ± 938 g. Overall recurrence rate for preeclampsia was 29% at a mean gestational age of 32 weeks. Thirty-eight women had an uncomplicated pregnancy (53%). The women with chronic hypertension had the highest recurrence rate of 38%. Neonatal mortality was 4%. CONCLUSION: The course of subsequent pregnancies after mid-trimester termination for preeclampsia is uncomplicated in 53% with a recurrence rate for preeclampsia of 29%. The mean gestational age at delivery was 11 weeks later and birth weight 2000 g higher than in the index pregnancy.

Cerebral autoregulation in different hypertensive disorders of pregnancy.

OBJECTIVE: Cerebrovascular complications that are associated with hypertensive disorders of pregnancy (preeclampsia, chronic hypertension [CHTN], and gestational hypertension [GHTN]) are believed to be associated with impaired cerebral autoregulation, which is a physiologic process that maintains blood flow at an appropriate level despite changes in blood pressure. The nature of autoregulation dysfunction in these conditions is unclear. We therefore evaluated autoregulation in 30 patients with preeclampsia, 30 patients with CHTN, and 20 patients with GHTN and compared them with a control group of 30 normal pregnant women. STUDY DESIGN: The autoregulatory index (ARI) was calculated with the use of simultaneously recorded cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler ultrasound), blood pressure (noninvasive arterial volume clamping), and end-tidal carbon dioxide during a 7-minute period of rest. ARI values of 0 and 9 indicate absent and perfect autoregulation, respectively. We use analysis of variance with Bonferroni test vs a control group. Data are presented as mean ± standard deviation. RESULTS: ARI was significantly reduced in preeclampsia (ARI, 5.5 ± 1.6; P = .002) and CHTN (ARI, 5.6 ± 1.7; P = .004), but not in GHTN (ARI, 6.7 ± 0.8; P = 1.0) when compared with control subjects (ARI, 6.7 ± 0.8). ARI was more decreased in patients with CHTN who subsequently experienced preeclampsia than in those who did not (ARI, 3.9 ± 1.9 vs 6.1 ± 1.2; P = .001). This was not true for women with GHTN or control subjects who later experienced preeclampsia. CONCLUSION: Pregnant women with CHTN or preeclampsia (even after exclusion of superimposed preeclampsia) have impaired autoregulation when compared with women with GHTN or normal pregnancy. Whether the decreased ARI in patients with CHTN who later experience preeclampsia is due to preexistent differences or early affected cerebral circulation remains to be determined.

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

OBJECTIVE: Women 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 DESIGN: Eighty-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. RESULTS: There 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. CONCLUSION: A 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.

Differential correlates of autobiographical memory specificity to affective and self-discrepant cues.

According to the CaRFAX model (Williams et al., 2007), several processes may result in overgeneral autobiographical memory. The present study examined whether the type of cue used in the Autobiographical Memory Test (AMT) is important for illuminating relationships between autobiographical memory specificity and variables pertinent to the Functional Avoidance (FA) and Capture and Rumination (CaR) aspects of the model. Sixty-one women varying in their experience of a potentially traumatic event and previous depression completed two versions of the AMT: one containing affective cues and the other containing cues representing idiosyncratic self-discrepancies. Consistent with the FA hypothesis, avoidance of the potentially traumatic event was associated with fewer specific memories on the affective, but not the self-discrepant AMT. Furthermore, in line with the CaR hypothesis, performance on the self-discrepant, but not the affective AMT was related to ruminative self-reflection in women reporting previous depression, even after controlling for current depression and education levels. Together the results suggest that varying cue type may increase the sensitivity of the AMT, depending on the aspect of the CaRFAX model of overgeneral memory that is to be addressed.

The effect of neuraxial anesthesia on maternal cerebral hemodynamics.

OBJECTIVE: Neuraxial anesthesia is known to reduce sympathetic tone and mean arterial pressure. Effects on cerebral hemodynamics in pregnancy are not well known. We hypothesize that cerebral hemodynamic parameters will change with respect to baseline following regional analgesia/anesthesia. STUDY DESIGN: We performed maternal transcranial Doppler of the middle cerebral artery in 20 women receiving epidural analgesia for labor, and 18 undergoing spinal anesthesia for cesarean section at baseline, 5 and 15 minutes. Systemic blood pressure (BP), systolic/diastolic/mean velocity, resistance and pulsatility index (PI) were recorded. Cerebral perfusion pressure, critical closing pressure (CrCP), resistance area product, and cerebral flow index were calculated. RESULTS: Epidural placement was associated with significant decreases in systolic/diastolic BP/mean velocity/CrCP after 15 minutes, with a corresponding increase in PI. In the spinal group, systolic/diastolic BP/mean velocity uniformly decreased and remained low after 15 minutes, and PI significantly increased and remained constant after 15 minutes. No differences were seen in BP or cerebral hemodynamics between the groups. CONCLUSION: This study demonstrates that both epidural analgesia and spinal anesthesia result in measurable cerebral hemodynamic changes in normotensive term pregnancy that are likely to be clinically insignificant as they do not affect perfusion pressure or flow.

The effect of low-dose oxytocin infusion on cerebral hemodynamics in pregnant women.

We investigated the cerebrovascular effects of continuous infusion of low-dose oxytocin in normal pregnant women undergoing induction of labor. In our prospective observational study, middle cerebral artery velocity was measured with transcranial Doppler ultrasound in 25 healthy, normotensive, nonsmoking patients undergoing induction of labor. No vasoactive drugs were used before or during the study period. Measurements were made at baseline and 15, 30, 60, and 120 minutes after oxytocin initiation. Mean arterial pressure, cerebral perfusion pressure, resistance index, resistance area product, and cerebral flow index at different times were calculated and compared using one-way analysis of variance (ANOVA) for repeated measures or Friedman repeated-measures ANOVA as appropriate, with P<0.05 regarded as significant. No significant systemic or cerebrovascular changes were noted after oxytocin initiation, and there was no correlation between the dosage administered and any hemodynamic parameter. Induction-dose oxytocin does not significantly affect selected cerebral hemodynamic parameters in the first 2 hours after initiation.

Neurocognitive functioning in women with a history of eclampsia: executive functioning and sustained attention.

Recently, information has emerged that formerly eclamptic women may suffer cognitive impairment. This may be related to cerebral white matter lesions. The few available reports demonstrate inconsistent results. We sought to elucidate cognitive performance after eclampsia in a pilot study. Twenty-six eclamptic, 20 preeclamptic, and 18 healthy parous women performed the Sustained Attention to Response Task (SART; the ability to sustain mindful processing of repetitive stimuli that would otherwise lead to habituation) and the Random Number Generation Task (RNG; executive functioning, i.e., inhibition and updating/monitoring). Average age was 40 years, elapsed time since index pregnancy was 9 years. Education levels did not differ. There were no intercurrent illnesses. No significant differences were found on SART and RNG scores between groups. This study was not able to demonstrate evidence for impaired sustained attention and executive functioning after eclampsia. Studies including a much wider range of neurocognitive tests amplified to posterior brain regions with larger groups are necessary.

Brain lesions several years after eclampsia.

OBJECTIVE: Eclampsia is thought to have no long-term neurological consequences. We aimed to delineate the neurostructural sequelae of eclampsia, in particular brain white matter lesions, utilizing high-resolution 3-Tesla magnetic resonance imaging (MRI). STUDY DESIGN: Formerly eclamptic women were matched for age and year of index pregnancy with normotensive parous controls. The presence and volume of brain white matter lesions were compared between the groups. RESULTS: MRI scans of 39 women who formerly had eclampsia and 29 control women were performed on average 6.4 +/- 5.6 years following the index pregnancy at a mean age of 38 years. Women with eclampsia demonstrated subcortical white matter lesions more than twice as often as compared with controls (41% vs 17 %; odds ratio, 3.3; 95% confidence interval, 1.05-10.61; P = .04). CONCLUSION: Cerebral white matter lesions occur more often in women who formerly had eclampsia compared with women with normotensive pregnancies. The exact pathophysiology underlying these imaging changes and their clinical relevance remain to be elucidated.

Mode of Delivery in Severe Preeclampsia Before 28 Weeks' Gestation: A Systematic Review.

IMPORTANCE: Preeclampsia with an onset before 28 weeks' gestation poses dilemmas for the obstetrician with regard to the mode of delivery. OBJECTIVE: The aim of this study was to analyze the success rate of attempted vaginal delivery and the maternal and neonatal outcome according to the mode of delivery in women with preeclampsia and an indicated delivery before 28 weeks' gestation. EVIDENCE ACQUISITION: A comprehensive search was performed in the bibliographic databases PubMed, Embase.com, and Wiley Cochrane Library. The main outcome was success rate of attempted vaginal delivery. Secondary outcomes were maternal and neonatal outcomes. RESULTS: Eight studies describing a total of 800 women were included. Success rates of vaginal delivery varied from 1.8% to 80%, and rates for cesarean delivery after induction of labor varied from 13% to 51%. The rates for planned cesarean delivery varied from 0% to 73%. Two studies (n = 53) described no statistical significant differences in maternal outcomes. Two other studies (n = 107) report no statistical difference in neonatal outcome. CONCLUSIONS: Studies that report the success rate of attempted vaginal delivery are limited in size. However, giving the available evidence in the reported studies a trial of labor is a considerable option in counseling women with a pregnancy complicated by preeclampsia before 28 weeks' gestation due to the similar maternal and neonatal outcome. No differences in maternal or neonatal outcome were attributed to the mode of delivery, however, numbers are small.

Induction of Labor for Maternal Indications at a Periviable Gestational Age; Survey on Management, Reporting and Auditing amongst Dutch Maternal-Fetal 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.

Self-reported cognitive functioning in formerly eclamptic women.

OBJECTIVE: Recently, persistent brain white matter lesions were demonstrated in eclamptic women when imaged 6 weeks after delivery. Moreover, many of these women complain about cognitive limitations years after the eclamptic pregnancy. Therefore, in a cohort of such women, we assessed cognitive failures in daily life. STUDY DESIGN: Thirty formerly eclamptic women completed the Cognitive Failures Questionnaire. Scores were compared with scores of formerly preeclamptic (n = 31) and healthy parous control participants (n = 30) with the use of a priori Student t test. Groups were matched in terms of current age and years elapsed since index pregnancy. RESULTS: Women who have had eclampsia scored significantly higher on the Cognitive Failures Questionnaire, compared with healthy parous control subjects (43.5 +/- 14.6 vs 36.1 +/- 13.9, respectively; P < .05). CONCLUSION: Women who have had eclampsia reported significantly more cognitive failures years after the index pregnancy. It is hypothesized that this might be due to some degree of cerebral white matter damage. This subjective assessment of cognitive function must be confirmed with objective neurocognitive testing and related to neuroimaging findings.

Preeclampsia: at risk for remote cardiovascular disease.

Epidemiological data indicate that women with preeclampsia are more likely to develop cardiovascular disease (CVD) later in life. Population-based studies relate preeclampsia to an increased risk of later chronic hypertension (RR, 2.00 to 8.00) and cardiovascular morbidity/mortality (RR, 1.3 to 3.07), compared with normotensive pregnancy. Women who develop preeclampsia before 36 weeks of gestation or have multiple hypertensive pregnancies are at highest risk (RR, 3.4 to 8.12). The underlying mechanism for the remote effects of preeclampsia is complex and probably multifactorial. Many risk factors are shared by CVD and preeclampsia, including endothelial dysfunction, obesity, hypertension, hyperglycemia, insulin resistance, and dyslipidemia. Therefore, it has been proposed that the metabolic syndrome may be a possible underlying mechanism common to CVD and preeclampsia. Follow-up and counseling of women with a history of preeclampsia may offer a window of opportunity for prevention of future 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.

Changes in cerebral autoregulation in the second half of pregnancy and compared to non-pregnant controls.

OBJECTIVE: The mechanism by which pregnancy affects the cerebral circulation is unknown, but it has a central role in the development of neurological complications in preeclampsia, which is believed to be related to impaired autoregulation. We evaluated the cerebral autoregulation in the second half of pregnancy, and compared this with a control group of healthy, fertile non-pregnant women. METHODS: In a prospective cohort analysis, cerebral blood flow velocity of the middle cerebral artery (determined by transcranial Doppler), blood pressure (noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were simultaneously collected for 7min. The autoregulation index (ARI) was calculated. ARI values of 0 and 9 indicated absent and perfect autoregulation, respectively. ANOVA and Pearson's correlation coefficient were used, with p<0.05 considered significant. RESULTS: A total of 76 pregnant and 18 non-pregnant women were included. The ARI did not change during pregnancy, but pregnant women had a significantly higher ARI than non-pregnant controls (ARI 6.7±0.9 vs. 5.3±1.4, p<0.001). This remained significant after adjusting for EtCO2 (p<0.001). CONCLUSION: Cerebral autoregulation functionality is enhanced in the second half of pregnancy, when compared to non-pregnant fertile women, even after controlling for EtCO2. The autoregulation does not change with advancing gestational age.

Terminating pregnancy for severe hypertension when the fetus is considered non-viable: a retrospective cohort study.

OBJECTIVE: To investigate frequency and practise of termination of pregnancy for early-onset hypertensive disorders where the fetus is considered to be non-viable. STUDY DESIGN: Retrospective cohort study in all Dutch tertiary perinatal care centres (n=10), between January 2000 and January 2014. All women who underwent termination of pregnancy, without fetal surveillance or intention to intervene for fetal reasons, for early-onset hypertensive disorders in pregnancy, were analyzed. Women eligible for this study were identified in the local delivery databases. Medical records were used to collect relevant data. RESULTS: Between January 2000 and January 2014, 2,456,584 women delivered in The Netherlands, of which 238,448 (9.7%) in a tertiary care centre. A total of 161 pregnancy terminations (11-12 per year) for severe early-onset preeclampsia were identified, including 6 women with a twin pregnancy. Mean gestational age at termination was 172 days (GA 244/7)±9.4 days. In 70% of cases termination was performed at or shortly after 24 weeks' gestation. 74.5% of women developed HELLP syndrome (n=96), eclampsia (n=10) or needed admission to an ICU (n=14). Birth weight was below 500g in 64% of cases. In 69% of the cases the estimated fetal weight was within a 10% margin of the actual birth weight. CONCLUSION: Termination of pregnancy for early-onset hypertensive disorders without intervention for fetal indication occurs approximately 12 times per year in The Netherlands. More data are needed to investigate contemporary best practice regarding termination of pregnancy for early-onset hypertensive indications at the limits of fetal viability. Considering the frequency of maternal complications, termination of pregnancy and not expectant management should be considered for all women presenting with severe early onset hypertensive disorders at the limits of fetal viability.

The effect of magnesium sulfate on large cerebral artery blood flow in preeclampsia.

OBJECTIVES: To determine the effect of a 6 gram intravenous bolus of magnesium sulfate on maternal cerebral blood flow in women with preeclampsia. STUDY DESIGN: Velocity-encoded phase-contrast magnetic resonance imaging studies were performed on twelve preeclamptic women prior to and immediately after infusion of a 6 gram magnesium sulfate loading dose. Cerebral blood flow was determined at the bilateral proximal middle and posterior cerebral arteries. Study participants returned 6 weeks postpartum for a non-pregnant measurement of cerebral blood flow. The Wilcoxon paired-sample test was used with statistical significance defined as p<0.05. RESULTS: There was no significant difference in cerebral vessel diameter nor blood flow for any of the examined arteries between the pre- and post magnesium sulfate therapy states. CONCLUSIONS: The absence of a significant difference in cerebral blood flow of the middle and posterior cerebral arteries before and after infusion of a 6 gram loading dose of magnesium sulfate in women with preeclampsia could suggest the absence of vasoconstriction of the large cerebral arteries in preeclampsia and question the role of magnesium sulfate as a vasodilator of these arteries.

Effect of breath holding on cerebrovascular hemodynamics in normal pregnancy and preeclampsia.

Preeclampsia (PE) is associated with endothelial dysfunction and impaired autonomic function, which is hypothesized to cause cerebral hemodynamic abnormalities. Our aim was to test this hypothesis by estimating the difference in the cerebrovascular response to breath holding (BH; known to cause sympathetic stimulation) between women with preeclampsia and a group of normotensive controls. In a prospective cohort analysis, cerebral blood flow velocity (CBFV) in the middle cerebral artery (transcranial Doppler), blood pressure (BP, noninvasive arterial volume clamping), and end-tidal carbon dioxide (EtCO2) were simultaneously recorded during a 20-s breath hold maneuver. CBFV changes were broken down into standardized subcomponents describing the relative contributions of BP, cerebrovascular resistance index (CVRi), critical closing pressure (CrCP), and resistance area product (RAP). The area under the curve (AUC) was calculated for changes in relation to baseline values. A total of 25 preeclamptic (before treatment) and 25 normotensive women in the second half of pregnancy were enrolled, and, 21 patients in each group were included in the analysis. The increase in CBFV and EtCO2 was similar in both groups. However, the AUC for CVRi and RAP during BH was significantly different between the groups (3.05 ± 2.97 vs. -0.82 ± 4.98, P = 0.006 and 2.01 ± 4.49 vs. -2.02 ± 7.20, P = 0.037), indicating an early, transient increase in CVRi and RAP in the control group, which was absent in PE. BP had an equal contribution in both groups. Women with preeclampsia have an altered initial CVRi response to the BH maneuver. We propose that this is due to blunted sympathetic or myogenic cerebrovascular response in women with preeclampsia.

Cerebral autoregulation in pregnancies complicated by diabetes and overweight.

AIM: The aim of this study was to estimate the impact of diabetes and obesity on cerebral autoregulation in pregnancy. METHODS: Cerebral autoregulation was evaluated in women with gestational diabetes, type 2 diabetes mellitus and/or overweight (body mass index ⩾ 25 kg m(-2)) and compared to a cohort of euglycaemic pregnant women. The autoregulation index was calculated using simultaneously recorded cerebral blood flow velocity in the middle cerebral artery and blood pressure. Autoregulation index values of 0 and 9 indicate absent and perfect autoregulation, respectively. RESULTS: Autoregulation index in women with either diabetes (n = 33, 6.6 ± 1.1) or overweight (n = 21, 6.7 ± 0.6) was not significantly different to that in control patients (n = 23, 6.6 ± 0.8, p = 0.96). CONCLUSION: Cerebral autoregulation is not impaired in pregnant women who have non-vasculopathic diabetes or overweight. This suggests that the increased risk of pre-eclampsia in diabetic and overweight women is not associated with early impaired cerebral autoregulation.

Inhibin-A and superimposed preeclampsia in women with chronic hypertension.

OBJECTIVE: To determine if maternal serum inhibin-A can be used as a marker for subsequent development of superimposed preeclampsia in women with chronic hypertension. METHODS: Serum for measurement of inhibin-A was obtained at monthly intervals in women with chronic hypertension requiring antihypertensive medications. Superimposed preeclampsia, the primary outcome of interest, was diagnosed when hypertensive women developed proteinuria (at least 300 mg per 24-hour urine specimen). Serum inhibin-A was considered abnormally elevated when the value exceeded the mean plus two standard deviations of the log for chronically hypertensive women who did not develop preeclampsia. RESULTS: A total of 61 women were enrolled in this study, and 21 (34%) developed superimposed preeclampsia. Inhibin-A levels increased with advancing gestational age. Ten women had abnormally increased inhibin-A levels; eight (80%) developed superimposed preeclampsia, compared with 13 of 51 (26%) women with normal inhibin-A levels (P <.001). Sensitivity and specificity were 38% and 95%, respectively, whereas the positive and negative predictive values were 80% and 75%, respectively. CONCLUSION: Although inhibin-A was abnormally increased an average of 3 weeks before the clinical onset of superimposed preeclampsia, the sensitivity of the test as a screen was too limited to be clinically useful.