Corine M. Koopmans

Accuracy of serum uric acid as a predictive test for maternal complications in pre-eclampsia: Bivariate meta-analysis and decision analysis

The aim of this study is to determine the accuracy and clinical value of serum uric acid in predicting maternal complications in women with pre-eclampsia. An existing meta-analysis on the subject was updated. The accuracy of serum uric acid for the prediction of maternal complications was assessed with a bivariate model estimating a summary Receiver Operating Characteristic (sROC) curve. Subsequently, a clinical decision analysis was performed, in which three alternative strategies were modelled: (I) expectant management with monitoring until spontaneous labour; (II) induction of labour; (III) serum uric acid as test for predicting maternal complications. In the latter strategy, accuracy data of serum uric acid derived from the sROC curve were used to assess the value of serum uric acid in the management of women with pre-eclampsia. In this strategy, women with an increased serum uric acid were supposed to have labour induced, whereas women with serum uric acid levels below the threshold were managed expectantly. The decision whether to use the policy expectant management, to induce labour or to test serum uric acid levels, is based on the expected utility of each strategy. The expected utility depends on the probability of occurrence of severe maternal complications (i.e. severe hypertension, haemolysis, elevated liver enzymes and low platelet count (HELLP syndrome) or eclampsia) and the mode of delivery (caesarean section versus vaginal delivery). Valuation of the outcomes was performed using a distress ratio, which expresses how much worse a complication of pre-eclampsia is valued as compared to a caesarean section. Eight studies, testing 1565 women with pre-eclampsia, met the inclusion criteria. If the distress ratio was 10, the strategy regarding serum uric acid would be the preferred strategy when the probability of complications was between 2.9 and 6.3%. At higher complication rates induction of labour would be preferred, whereas at lower complication rates expectant management would be the best treatment option. These findings were stable in sensitivity analyses, using different distress ratios. Based on the decision analysis, serum uric acid seems to be a useful test in the management of pre-eclampsia under realistic assumptions.

Induction of labour versus expectant monitoring in women with pregnancy induced hypertension or mild preeclampsia at term: the HYPITAT trial

BackgroundHypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates.Methods/DesignWomen with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%.DiscussionThis trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications.Trial RegistrationThe protocol is registered in the clinical trial register number ISRCTN08132825.

Accuracy of liver function tests for predicting adverse maternal and fetal outcomes in women with preeclampsia : a systematic review

Background. Liver function tests are routinely performed in women as part of a battery of investigations to assess severity at admission and later to guide appropriate management. Objective. To determine the accuracy with which liver function tests predict complications in women with preeclampsia by a systematic review. Data. We conducted electronic searches without language restrictions in (1951–2010), (1980–2010) and the Cochrane Library (2009). Methods of Study Selection. Primary articles that evaluated the accuracy of liver function tests in predicting complications in women with preeclampsia were chosen. Data was extracted by two reviewers independently. A bivariate model estimated area under the curve, sensitivity and specificity. Results. There were 13 primary articles including a total of 3 497 women assessing maternal (30 2×2 tables) and fetal (19 2×2 tables) outcomes. For predicting adverse maternal outcome, the point estimates of specificity were >70% in 18 tables with 0.79 (95%CI 0.51, 0.93). For predicting adverse fetal outcomes the specificity of the test was >70% in 2×2 tables. Sensitivity of the test was poor for both maternal and fetal outcomes. Conclusion. In women with preeclampsia, function tests performed better in predicting adverse maternal than fetal outcomes. The presence of increased liver enzymes was associated with an increased probability of maternal and fetal complications, but normal liver enzyme levels did not rule out disease, as specificity was often higher than sensitivity.

Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre-eclampsia at term? An exploratory analysis of the HYPITAT trial

Please cite this paper as: Tajik P, van der Tuuk K, Koopmans C, Groen H, van Pampus M, van der Berg P, van der Post J, van Loon A, de Groot C, Kwee A, Huisjes A, van Beek E, Papatsonis D, Bloemenkamp K, van Unnik G, Porath M, Rijnders R, Stigter R, de Boer K, Scheepers H, Zwinderman A, Bossuyt P, Mol B. Should cervical favourability play a role in the decision for labour induction in gestational hypertension or mild pre‐eclampsia at term? An exploratory analysis of the HYPITAT trial. BJOG 2012;119:1123–1130.

Abnormal endothelium-dependent microvascular dilator reactivity in pregnancies complicated by normotensive intrauterine growth restriction

OBJECTIVE Normotensive intrauterine growth restriction and preeclampsia share a similar placenta pathophysiology, whereas maternal clinical manifestations differ. Clinical symptoms of preeclampsia are partly attributed to vascular endothelial dysfunction, but it is unclear whether this phenomenon plays a role in intrauterine growth restriction. Therefore, we investigated microvascular endothelial function in women with intrauterine growth restriction. STUDY DESIGN Laser Doppler fluxmetry was used combined with iontophoresis of acetylcholine and sodium nitroprusside, namely, endothelium-dependent and endothelium-independent vasodilators. We studied 12 women with intrauterine growth restriction and 16 controls in the third trimester of pregnancy. All women had prepregnancy body mass indexes < 26. RESULTS Acetylcholine-mediated vasodilatation was significantly increased in women with intrauterine growth restriction compared with controls (743% +/- 120% vs 390% +/- 67%, P = .01); sodium nitroprusside-mediated vasodilatation was not different (360% +/- 55% vs 363% +/- 65%, P > .99). CONCLUSION Nonobese women with normotensive intrauterine growth restriction show abnormal endothelium-dependent microvascular vasodilatation, suggesting endothelial dysfunction as in preeclampsia. Obviously, for the clinical manifestation of preeclampsia additional factors are required, and a role of metabolic syndrome and obesity has been suggested.

Determinants of health-related quality of life in the postpartum period after obstetric complications

OBJECTIVE To determine the influence of socio-demographic, clinical parameters and obstetric complications on postpartum health-related quality of life (HRQoL). STUDY DESIGN We used data of three randomized controlled trials to investigate HRQoL determinants in women after an obstetric complication. The DIGITAT and HYPITAT trials compared induction of labor and expectant management in women with intra-uterine growth restriction (IUGR) and hypertensive disorders. The WOMB trial randomized anemic women after postpartum hemorrhage to red blood cell transfusion or expectant management. The HRQoL-measure Short-Form36 was completed at six weeks postpartum. Multivariable analyses were used to identify which parameters affected the Short-Form36 physical component score (PCS) and mental component score (MCS). RESULTS HRQoL analyses included 1391 women (60%) of the 2310 trial participants. HYPITAT and DIGITAT participants had significantly lower MCS than WOMB participants. In multivariable analysis, PCS after elective and emergency cesarean section was 5-6 points lower than after vaginal delivery. Gestational hypertension, neonatal admission and delivery in an academic hospital had a small negative effect on PCS. No effect was found for randomization status, maternal age, BMI, country of birth, education, parity, induction of labor, analgesics, birth weight, perineal laceration, delivery of placenta, postpartum hemorrhage, congenital anomaly, urinary tract infection, thromboembolic event or endometritis. MCS was influenced only mildly by these parameters. CONCLUSIONS IUGR and hypertensive disorders lead to lower HRQoL scores postpartum than PPH. In a heterogeneous obstetric population, only mode of delivery by cesarean section has a profound, negative impact, on physical HRQoL (PCS). No profound impacts on MCS were detected.

Prediction of progression to a high risk situation in women with gestational hypertension or mild pre-eclampsia at term

Objective:  To evaluate whether progression to a high‐risk situation is predictable in women with gestational hypertension (GH) or mild pre‐eclampsia (PE) at term.

Impact of the HYPITAT trial on doctors’ behaviour and prevalence of eclampsia in the Netherlands

Please cite this paper as: van der Tuuk K, Koopmans C, Groen H, Mol B, van Pampus M for the HYPITAT study group. Impact of the HYPITAT trial on doctors’ behaviour and prevalence of eclampsia in the Netherlands. BJOG 2011;118:1658–1660.

Health-related quality of life after induction of labor versus expectant monitoring in gestational hypertension or preeclampsia at term.

Objective. Gestational hypertension (GH) and preeclampsia (PE) are major contributors to maternal and neonatal morbidity and mortality. In GH or PE, labor may be either induced or monitored expectantly. We studied maternal health-related quality of life (HR-QoL) after induction of labor versus expectant monitoring in GH or PE at term. We performed the HR-QoL study alongside a multicenter randomized controlled trial comparing induction of labor to expectant monitoring in women with GH or PE after 36 weeks. Methods. We used written questionnaires, covering background characteristics, condition-specific issues, and validated measures: the Short-Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression Scale (HADS), and Symptom Checklist (SCL-90). Measurements were at the following time points: baseline, 6 weeks postpartum, and 6 months postpartum. A multivariate mixed model with repeated measures was defined to assess the effect of the treatments on the physical component score (PCS) and mental component score (MCS) of the SF-36. Analysis was by intention to treat. Results. We analyzed the data of 491 randomized and 220 nonrandomized women. We did not find treatment effect on long-term HR-QoL (PCS: p = 0.09; MCS: p = 0.82). The PCS improved over time (p < 0.001) and was better in nonrandomized patients (p = 0.02). Conclusion. Despite a clinical benefit of induction of labor, long-term HR-QoL is equal after the induction of labor and expectant management in women with GH or PE beyond 36 weeks of gestation.

Risk indicators for eclampsia in gestational hypertension or mild preeclampsia at term.

Objective. To evaluate whether eclampsia can be predicted in gestational hypertension or mild preeclampsia at term. Methods. For this case–control study we selected 76 cases with eclampsia from the LEMMoN study and 1149 controls with mild hypertensive disease of pregnancy, who did not develop eclampsia, from the HYPITAT study. Risk indicators for eclampsia, identified in multivariable logistic regression, were used to assess the predictive capacity of our model with receiver-operating characteristic (ROC) curve analysis. Model optimism was assessed with bootstrapping. Results. Maternal age, non-Caucasian ethnicity, systolic blood pressure >155 mmHg, ≥2+ protein on dipstick, elevated uric acid, creatinin >74 μmol/L, aspartate aminotransferase >30 U/L, and lactate dehydrogenase >400 U/L were significantly associated with eclampsia. Other factors included in the model were previous fetal loss, previous miscarriage, gestational age, and low platelet count. The area under the ROC curve was 0.92. Bootstrapping showed minimal overfitting of the model. Conclusion. In women with gestational hypertension or mild preeclampsia at term eclampsia can be predicted.