Cost-effectiveness of diagnostic testing strategies including cervical-length measurement and fibronectin testing in women with symptoms of preterm labor.

OBJECTIVE: To evaluate the cost-effectiveness of combining cervical-length (CL) measurement and fetal fibronectin (fFN) testing in women with symptoms of preterm labor between 24 and 34 weeks' gestation. METHODS: This was a model-based cost-effectiveness analysis evaluating seven test-treatment strategies based on CL measurement and/or fFN testing in women with symptoms of preterm labor from a societal perspective, in which neonatal outcomes and costs were weighted. Estimates of disease prevalence, test accuracy and costs were based on two recently performed nationwide cohort studies in The Netherlands. RESULTS: Strategies using fFN testing and CL measurement separately to predict preterm delivery are associated with higher costs and incidence of adverse neonatal outcomes compared with strategies that combine both tests. Additional fFN testing when CL is 15-30 mm was considered cost effective, leading to a cost saving of €3919 per woman when compared with a treat-all strategy, with a small deterioration in neonatal health outcomes, namely one additional perinatal death and 21 adverse outcomes per 10 000 women with signs of preterm labor (incremental cost-effectiveness ratios €39 million and €1.9 million, respectively). Implementing this strategy in The Netherlands, a country with about 180 000 deliveries annually, could lead to an annual cost saving of between €2.4 million and €7.6 million, with only a small deterioration in neonatal health outcomes. CONCLUSION: In women with symptoms of preterm labor at 24-34 weeks' gestation, performing additional fFN testing when CL is between 15 and 30 mm is a viable and cost-saving strategy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Maternal and neonatal outcomes in women with severe early onset pre-eclampsia before 26 weeks of gestation, a case series.

OBJECTIVE: To describe the maternal and neonatal outcomes and prolongation of pregnancies with severe early onset pre-eclampsia before 26 weeks of gestation. DESIGN: Nationwide case series. SETTING: All Dutch tertiary perinatal care centres. POPULATION: All women diagnosed with severe pre-eclampsia who delivered between 22 and 26 weeks of gestation in a tertiary perinatal care centre in the Netherlands, between 2008 and 2014. METHODS: Women were identified through computerised hospital databases. Data were collected from medical records. MAIN OUTCOME MEASURES: Maternal complications [HELLP (haemolysis, elevated liver enzyme levels, and low platelet levels) syndrome, eclampsia, pulmonary oedema, cerebrovascular incidents, hepatic capsular rupture, placenta abruption, renal failure, and maternal death], neonatal survival and complications (intraventricular haemorrhage, retinopathy of prematurity, necrotising enterocolitis, bronchopulmonary dysplasia, and sepsis), and outcome of subsequent pregnancies (recurrent pre-eclampsia, premature delivery, and neonatal survival). RESULTS: We studied 133 women, delivering 140 children. Maternal complications occurred frequently (54%). Deterioration of HELLP syndrome during expectant care occurred in 48%, after 4 days. Median prolongation was 5 days (range: 0-25 days). Neonatal survival was poor (19%), and was worse (6.6%) if the mother was admitted before 24 weeks of gestation. Complications occurred frequently among survivors (84%). After active support, neonatal survival was comparable with the survival of spontaneous premature neonates (54%). Pre-eclampsia recurred in 31%, at a mean gestational age of 32 weeks and 6 days. CONCLUSIONS: Considering the limits of prolongation, women need to be counselled carefully, weighing the high risk for maternal complications versus limited neonatal survival and/or extreme prematurity and its sequelae. The positive prospects regarding maternal and neonatal outcome in future pregnancies can supplement counselling. TWEETABLE ABSTRACT: Severe early onset pre-eclampsia comes with high maternal complication rates and poor neonatal survival.

Quantitative fetal fibronectin testing in combination with cervical length measurement in the prediction of spontaneous preterm delivery in symptomatic women.

OBJECTIVE: To evaluate whether in symptomatic women, the combination of quantitative fetal fibronectin (fFN) testing and cervical length (CL) improves the prediction of preterm delivery (PTD) within 7 days compared with qualitative fFN and CL. DESIGN: Post hoc analysis of frozen fFN samples of a nationwide cohort study. SETTING: Ten perinatal centres in the Netherlands. POPULATION: Symptomatic women between 24 and 34 weeks of gestation. METHODS: The risk of PTD <7 days was estimated in predefined CL and fFN strata. We used logistic regression to develop a model including quantitative fFN and CL, and one including qualitative fFN (threshold 50 ng/ml) and CL. We compared the models' capacity to identify women at low risk (<5%) for delivery within 7 days using a reclassification table. MAIN OUTCOME MEASURES: Spontaneous delivery within 7 days after study entry. RESULTS: We studied 350 women, of whom 69 (20%) delivered within 7 days. The risk of PTD in <7 days ranged from 2% in the lowest fFN group (<10 ng/ml) to 71% in the highest group (>500 ng/ml). Multivariable logistic regression showed an increasing risk of PTD in <7 days with rising fFN concentration [10-49 ng/ml: odds ratio (OR) 1.3, 95% confidence interval (95% CI) 0.23-7.0; 50-199 ng/ml: OR 3.2, 95% CI 0.79-13; 200-499 ng/ml: OR 9.0, 95% CI 2.3-35; >500 ng/ml: OR 39, 95% CI 9.4-164] and shortening of the CL (OR 0.86 per mm, 95% CI 0.82-0.90). Use of quantitative fFN instead of qualitative fFN resulted in reclassification of 18 (5%) women from high to low risk, of whom one (6%) woman delivered within 7 days. CONCLUSION: In symptomatic women, quantitative fFN testing does not improve the prediction of PTD within 7 days compared with qualitative fFN testing in combination with CL measurement in terms of reclassification from high to low (<5%) risk, but it adds value across the risk range. TWEETABLE ABSTRACT: Quantitative fFN testing adds value to qualitative fFN testing with CL measurement in the prediction of PTD.

Pregnancy outcomes in women with heart disease: Experience of a tertiary center in the Netherlands.

OBJECTIVES: Clinical data of pregnant women with heart disease were obtained with the intention to provide input for local counseling and management guidelines. STUDY DESIGN: Retrospective data from all pregnant women with congenital or acquired heart disease between 2000 and 2011 in the VU University Medical Centre Amsterdam. MAIN OUTCOME MEASURES: Maternal and neonatal outcomes were evaluated. RESULTS: Data of 122 women with 160 pregnancies were obtained. The most common heart diseases were congenital heart disease (n=65, 53.3%) and arrhythmia (n = 20, 16.4%). Based on the functional criteria of the New York Heart Association (NYHA), 114/122 patients (93.4%) were classified NYHA class I-II. Patients in NYHA class III-IV (n = 8/122, 6.6%), mainly had a history of myocardial infarction or pulmonary hypertension. There were 156 singleton and 4 twin pregnancies. 22 (13.5%) pregnancies were complicated by hypertensive disorders. Heart failure developed in 11 women (9.0%), 37.5% in NYHA class III-IV and 6.5% in NYHA class I-II. Mean gestational age and birth weight were 270 days and 3196 g in NYHA class I-II compared to 237 days and 1972 g for NHYA class III-IV. There were two maternal deaths (1.6%) and 5 fetal deaths (3.1%). There were 29 (12.8%) preterm births, 20 (12.8%) neonates small for gestational age and 34 (21.8%) admittances on the Neonatal Intensive Care Unit (NICU). CONCLUSIONS: Pregnancy in women with pre-existing heart disease in all NYHA classes is associated with increased maternal morbidity and perinatal morbidity. Risk of structural fetal anomalies is especially high in women with congenital heart disease.

Termination of pregnancy for maternal indications at the limits of fetal viability: a retrospective cohort study in the Dutch tertiary care centres.

OBJECTIVE: Maternal morbidity, either pregnancy related or pre-existent, can become life threatening and of such severity as to warrant termination of pregnancy (TOP). In this situation, chances of fetal survival are usually poor, either because of low gestational age and/or because of the fetal effects of the maternal condition. Examples include severe growth restriction in pre-eclampsia and intrauterine infection due to the very early preterm prelabour rupture of membranes. There are very few reports on the prevalence of TOP for maternal indication at the limits of fetal viability. We investigated the prevalence of and indications for TOP on maternal indication in the 10 tertiary care centres in the Netherlands during the past decade. STUDY DESIGN: We conducted a retrospective review of the medical records of all women who underwent TOP for maternal indications between 22 and 27 completed weeks of gestation in all 10 tertiary care centres from 2000 to 2009. RESULTS: During the study period, there were 1 929 470 deliveries; 163 052 (8.4%) of these took place in one of the 10 tertiary care centres and 177 pregnancies were terminated for severe maternal disease, 131 for hypertensive disorders, 29 for intrauterine infection and 17 for other reasons. The mean gestational age at TOP was 171 days (24(3/7))±10 days. No maternal deaths were recorded. The overall perinatal mortality was 99.4%. CONCLUSIONS: Over a 10-year period, TOP for maternal indications was performed in 1 in 1000 deliveries in the 10 Dutch tertiary care centres. Hypertensive disorders comprised three-quarters of the cases.

Peri-partum reference ranges for ROTEM(R) thromboelastometry.

BACKGROUND: Post-partum haemorrhage (PPH) causes rapidly developing deficiencies in clotting factors and contributes to substantial maternal morbidity and mortality. Rotational thromboelastometry (ROTEM(®)) is increasingly used as a point of care coagulation monitoring device in patients with massive haemorrhage; however, there are limited data on reference ranges in the peri-partum period. These are required due to the haemostatic changes in pregnancy. METHODS: In a Dutch multi-centre trial, 161 subjects were included; blood samples were obtained during labour (T1) and within 1 h of delivery (T2). Reference ranges of ROTEM(®) INTEM, EXTEM, FIBTEM, and APTEM were set and correlation with laboratory results was investigated using the guidelines of the International Federation of Clinical Chemistry. RESULTS: Reference ranges were obtained for clotting time (CT), clot formation time (CFT), α-angle, clot firmness at 10 and 20 min (A10, A20), maximum clot firmness (MCF), and maximum lysis (ML). These were comparable from centre to centre, and between T1 and T2. Reference ranges T1: EXTEM: CT 31-63 s, CFT 41-120 s, and MCF 42-78 mm. INTEM: CT 109-225 s, CFT 40-103, and MCF 63-78 mm. FIBTEM: CT 31-79 s and MCF 13-45 mm. APTEM: CT 33-62 s, CFT 42-118, and MCF 61-79 mm. CONCLUSIONS: Reference values for ROTEM(®) parameters are reported. The previously published correlation between FIBTEM parameters and plasma fibrinogen levels by the Clauss method is confirmed. Further research is needed to define threshold values for haemostatic therapy in the course of PPH. Clinical trial registration NTR 2515 (http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2515).

Is intrapartum fever associated with ST-waveform changes of the fetal electrocardiogram? A retrospective cohort study.

OBJECTIVE: To investigate the association between maternal intrapartum fever and ST-waveform changes of the fetal electrocardiogram. DESIGN: Retrospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: We studied 142 women with fever (≥38.0°C) during labour and 141 women with normal temperature who had been included in two previous studies. In both groups, we counted the number and type of ST-events and classified them as significant (intervention needed) or not significant, based on STAN(®) clinical guidelines. MAIN OUTCOME MEASURES: Number and type of ST-events. RESULTS: Both univariable and multivariable regression analysis showed no association between the presence of maternal intrapartum fever and the number or type of ST-events. CONCLUSIONS: Maternal intrapartum fever is not associated with ST-segment changes of the fetal electrocardiogram. Interpretation of ST-changes in labouring women with fever should therefore not differ from other situations.

PP150. Pregnancy outcome in women with heart disease in a single tertiary care center.

INTRODUCTION: The number of women presenting with cardiac disease during pregnancy is increasing because more women with repaired congenital heart disease are reaching childbearing age and because of more pregnancies occurring in women with ischemic heart disease. Cardiac disease is the leading cause of indirect maternal mortality in the Netherlands. OBJECTIVES: Clinical data of pregnant women with heart disease that received obstetric care and delivered in our center have been obtained with the intention to evaluate the cardiac and obstetric pregnancy outcomes and to provide data for local counseling and management guidelines. METHODS: Data were collected from all pregnant women with congenital or acquired heart disease who delivered between 2000 and 2010 in the VU University Medical Center Amsterdam. At least one consultation of a cardiologist during pregnancy was advised. The maternal outcomes of these pregnancies were evaluated. RESULTS: Data of 122 women with 160 pregnancies were obtained. In this study the main heart diseases in pregnancy were congenital heart disease (n=75.61%) and arrhythmia (n=22.18%). Rheumatic heart disease was accountable for 6% (n=7) and ischemic heart disease for 4% (n=5) of inclusions. Based on the functional criteria of the New York Heart Association (NYHA), 114/122 patients (93.4%) were classified NYHA Class I-II. Patients in NYHA Class III-IV (n=8/122, 6.6%), mainly had a history of myocardial infarction or pulmonary hypertension. Of all the women, 35 had cardiac surgery before pregnancy, mainly repair of congenital heart disease. In women with acquired heart disease the interventions before pregnancy included permanent cardiac pace-maker implantation (n=2), radiofrequency catheter ablation (RFCA) (n=4) and percutaneous transluminal coronary angioplasty or coronary artery bypass graft (n=4). There were 156 singleton and 4 twin pregnancies. Termination of pregnancy was performed in 3 cases; 1 for maternal cardiac and 2 for obstetric indications. There were 156 life-births of which 100 (64.1%) were spontaneous vaginal deliveries, 17 (10.9%) operative vaginal deliveries and 39 (25%) cesarean sections: 9 for maternal cardiac indication and 30 for obstetric reasons. 36 (36%) women received epidural analgesia during labor and delivery. Cesarean section under general anesthesia was performed in 14 cases (7 for maternal cardiac indication); 25 were performed under spinal/epidural anesthesia. Induction of labour occurred in 48 pregnancies: 10 for maternal cardiac indications and 38 for other maternal and fetal indications. 28 (17.5%) pregnancies were complicated by hypertensive disorders. Cardiac complications such as heart failure developed in 15 (9.4%) pregnancies. There were two maternal deaths (1.6%). CONCLUSION: Congenital heart disease is the type of heart disease that has the highest incidence in pregnancy, while main types of heart disease that lead to impaired cardiac function during pregnancy are ischemic disease and pulmonary hypertension. Incidence of pregnancy induced hypertensive disorders is increased in women with preexistent cardiac disorders. Maternal outcome is generally favourable for women with cardiac heart in NYHA class I/II.

Fetal blood sampling in addition to intrapartum ST-analysis of the fetal electrocardiogram: evaluation of the recommendations in the Dutch STAN® trial.

OBJECTIVES: To evaluate the recommendations for additional fetal blood sampling (FBS) when using ST-analysis of the fetal electrocardiogram. DESIGN: Prospective cohort study. SETTING: Three academic and six non-academic teaching hospitals in the Netherlands. POPULATION: Labouring women with a high-risk singleton pregnancy in cephalic position beyond 36 weeks of gestation. METHODS: In labouring women allocated to the STAN® arm of a previously published randomised controlled trial who underwent one or more FBS during delivery, we assessed whether FBS was performed according to the trial protocol and how fetal acidosis, defined as an FBS pH < 7.20, was related to ST-waveform analysis. MAIN OUTCOME MEASURES: The number of FBS showing fetal acidosis, related to the different STAN® criteria where additional FBS is recommended. RESULTS: Among 2827 women monitored with STAN®, 297 underwent FBS, of whom 171 (57.6%) were performed according to the predefined criteria and 126 were performed in absence of these criteria. In the first group, rates of fetal acidosis (pH < 7.20) were two of 18, none of nine, 12 of 111 and three of 33 when FBS was taken for abnormal cardiotocogram (CTG) at the start, intermediary CTG at the start, abnormal CTG >60 minutes, and poor electrocardiogram quality, respectively. When the predefined criteria were not met and ST-analysis showed no ST-events, only two incidents of fetal acidosis were seen. CONCLUSIONS: The performance of FBS is valuable in the advised STAN® criteria. When these criteria are not met, performance of FBS does not seem helpful in the detection of fetal acidosis.

Electrical cardioversion during pregnancy: safe or not?

Two pregnant patients with a sustained symptomatic maternal supraventricular arrhythmia are presented. Both patients were treated with direct-current cardioversion. Electrical cardioversion during pregnancy is a rarely applied but highly effective procedure in the treatment of maternal cardiac arrhythmias and is assumed safe for both mother and child. However, once foetal viability is reached, monitoring of the foetal heart rate is advised and facilities for immediate caesarean section should be available.

[Tertiary obstetric care: the aims of the planning decree on perinatal care of 2001 have not yet been achieved]. / Derdelijns verloskundige zorg: doelstellingen van het 'planningsbesluit bijzondere perinatologische zorg' uit 2001 nog niet gehaald.

OBJECTIVE: To compare the actual situation in tertiary perinatal care in the Netherlands with the objectives laid down in the 2001 decree on perinatal care by the Dutch Ministry of Health, Welfare and Sport. DESIGN: Descriptive, retrospective. METHOD: Data on tertiary perinatal care, the transfer or refusal of women with very endangered pregnancies and the personnel of obstetric high care (OHC) units in 2006 were compared with the targets laid down in the planning decree on perinatal care and in a report by the Dutch Health Council from 2000. Parameters of tertiary perinatal care output were the number of admissions, and the number of beds in OHC units and neonatal intensive care units (NICU). RESULTS: In 2006, 128 of the 250 beds intended for OHC had been obtained. The degree of capacity utilisation was 94%, while the norm is 80%. 312 women were transferred due to lack of capacity of OHC units and NICU. The number of staff, specialised physicians as well as nurses, was considerably lower than the planned capacity. But training for obstetric perinatologists and OHC nurses was given. CONCLUSION: The targets for the number of beds for tertiary obstetric care and associated medical personnel have not been achieved as yet. As a consequence, the number of transfers is still too high. The funding of OHC units is not attuned to the complexity of tertiary perinatal care. Closer supervision of the execution of the planning decree and an adequate financing system are needed to achieve the objectives of the planning decree in the next 3 years.

Color Doppler ultrasound of spiral artery blood flow for prediction of hypertensive disorders and intra uterine growth restriction: a longitudinal study.

OBJECTIVE: To construct reference ranges for spiral artery (SA) flow velocities and examine the possibility to predict intra uterine growth restricted (IUGR) fetuses, pregnancy-induced hypertension (PIH) and/or preeclampsia. METHODS: Spiral artery flow velocity measurements were performed using Color Doppler between 11 to 13 + 6, between 14 to 17 + 6 and between 18 to 24 weeks of gestation, each measurement was performed twice. Spiral artery flow velocities were analyzed with multilevel modeling: individual regression curves were estimated and combined to obtain the reference intervals for SA flow velocities in normal pregnancies. Mann-Whitney U tests was used to compare the deviation from expected flow velocity between normal and complicated pregnancies. RESULTS: One hundred and eight pregnancies were included; 4 pregnancies were complicated with preeclampsia, 10 pregnancies with IUGR fetuses (

[Indications for respiratory complications during the use of oral nifedipine as a tocolytic agent, especially in patients with multiple pregnancies]. / Aanwijzingen voor respiratoire complicaties bij gebruik van oraal nifedipine als tocolyticum, met name bij patiënten met een meerlingzwangerschap.

In 7 women with premature labour pains, severe dyspnoea developed that was possibly related to the use of nifedipine as an 'off-label' tocolytic. 6 of these women had a twin pregnancy. Diuretics and oxygen therapy had little effect, but the patients recovered after the administration of nifedipine was stopped. The efficacy and safety of nifedipine as a tocolytic agent has been investigated in a number of well-designed randomised studies. However, these studies were performed in a selected group of pregnant women and women with multiple pregnancies or prematurely ruptured membranes were mostly excluded. It can be hypothesised that the respiratory complications in these cases are due to unequal ventilation/perfusion of the lungs in the presence of a physiologically elevated diaphragm due to the pregnancy. These changes are more pronounced in multiple pregnancies. After administration ofnifedipine, there is perfusion of atelectatic areas of the lung that are not or not well ventilated, resulting in ventilation-perfusion discrepancy and hence dyspnoea. Although case reports permit only limited extrapolation, these observations warrant caution with regard to the safety ofnifedipine as a tocolytic agent in patients with multiple pregnancies. The use of medication in groups of patients for which the agent has not been investigated, or which were explicitly excluded from the study, should be done with extreme caution. One should in any case be aware of the possible risks.

Pharmacological and surgical therapy for primary postpartum hemorrhage.

Early postpartum hemorrhage remains a significant cause of maternal morbidity and mortality. Postpartum hemorrhage is most commonly due to uterine atony and often responds to medical treatments such as administration of uterotonic drugs, alone or in combination with uterine massage or bimanual compression. As the incidence of cesarean section continues to rise, the problem of placenta previa and accreta is likely to become more common. For first-line management of postpartum hemorrhage adequate blood and fluid replacement is mandatory. In recent years new therapeutic measures to control the bleeding have gained attention. Although, these newer therapies focus on avoiding the need for emergency hysterectomy and preservation of reproductive function, reports of subsequent pregnancies are still scarce. Established management options are shortly reviewed and novel medical and surgical treatments are more extensively discussed.

Management and monitoring of severe preeclampsia.

Preeclampsia is associated with increased maternal and perinatal morbidity and mortality. Preeclampsia is more than pregnancy-induced hypertension. The hypertension is only one manifestation of an underlying multifactorial, multisystem disorder, initiated early in pregnancy. In established severe disease there is volume contraction, reduced cardiac output, enhanced vascular reactivity, increased vascular permeability and platelet consumption. Medical treatment of severe hypertension in pregnancy is required. The more controversial issues are the role of pharmacological treatment in conservative management of severe preeclampsia aiming at prolongation of pregnancy, the ability of such therapy to modify the course of the underlying systemic disorder and the effects on fetal and maternal outcome. This paper presents an overview concerning the current developments in management and monitoring of severe preeclampsia. Controversial topics such as the role of plasma volume expansion in preeclampsia, expectant versus aggressive management of severe preeclampsia remote from term, and pharmacological interventions in the management of eclampsia and the HELLP syndrome are addressed.

Pathophysiology of preeclampsia and the role of serotonin.

Hypertensive disorders constitute the most common medical complications of pregnancy. In normal pregnancy, impressive physiological changes take place in the maternal cardiovascular system. Morphological changes are the result of invasion of migratory trophoblast cells into the walls of the spiral arteries. After destruction of elastic, muscular and neural tissue in the media, the trophoblast cells get incorporated into the vessel wall and the endothelial lining of the spiral arteries is restored. The physiological changes create a low-resistance, low-pressure, high-flow system with the absence of maternal vasomotor control. Biochemical adaptations in maternal vasculature include changes in the prostaglandin system, the renin-angiotensin-aldosteron system and the kallikrein-kinin system. In preeclampsia, physiological changes in the spiral arteries are confined to the decidual portion of the arteries. Myometrial segments remain anatomically intact and fail to dilate. In addition, the adrenergic nerve supply is left intact. The cause of this impaired endovascular trophoblast invasion is not yet elucidated. But in combination with the imbalance between vasodilator and vasoconstrictor eicosanoids, it gives rise to reduced perfusion of the intervillous space. In the absence of an adequate production of antiaggregatory prostacyclin (PGI(2)), nitric oxide, or both, surface-mediated platelet activation is supposed to occur on the surface of the spiral arteries. Because platelets are the principal source of circulating serotonin, the increased platelet aggregation in preeclampsia causes an increase in serotonin levels. Interaction of serotonin with serotonin(1)- or serotonin(2)-receptors depends on the state of the endovascular trophoblast or endothelium in the spiral arteries and has opposite effects with regard to vasodilating and vasoconstrictive influences.

Pharmacological treatment of severe hypertension in pregnancy and the role of serotonin(2)-receptor blockers.

Hypertensive disorders of pregnancy are the leading cause of maternal and perinatal mortality and morbidity in developing and developed countries. The etiology of preeclampsia is still unknown. Delivering the baby is the only definite treatment. The benefits of acute pharmacological control of severe hypertension prior to and/or post-delivery are generally accepted. Most drugs commonly used in the management of severe hypertension in pregnancy have significant maternal and/or neonatal adverse side effects. Furthermore, some are not effective to acutely lower the blood pressure in patients with a hypertensive crisis. Until recently not one of the commonly used antihypertensive drugs has been tailored to the pathophysiology of severe preeclampsia, being a clinical syndrome characterized by endothelial cell dysfunction, vasospasm and platelet aggregation. Ketanserin, a serotonin(2)-receptor blocker, is a drug that appears to be tailored for treating this pregnancy-associated enthothelial cell dysfunction. The results of several prospective trials show that there is a definite place for serotonin(2)-receptor blockers in the treatment of pregnancy-induced hypertensive disorders. This review provides a summary on the more established drugs as well as on some of the newer antihypertensive drugs used in pregnancy with emphasis on the existing experience with ketanserin.

Ketanserin for the treatment of preeclampsia.

OBJECTIVE: To compare maternal and perinatal outcome with the use of either intravenous ketanserin or dihydralazine in treatment of women with preeclampsia. METHODS: The records from January 1989 to January 1997 of all patients receiving intravenous ketanserin or dihydralazine as first line antihypertensive therapy were reviewed and standardized data forms were completed. 315 charts of patients were identified and evaluated for effects on blood pressure, laboratory parameters, maternal and perinatal outcome. RESULTS: During the study interval 169 patients received ketanserin and 146 dihydralazine. Significantly fewer antepartum (27% versus 38%, p = 0.04) and postpartum (25% versus 39%, p = 0.01) maternal complications were noted in patients receiving ketanserin. Occurrence of HELLP syndrome was significantly lower among patients who received ketanserin (20%) than among those who received dihydralazine (40%, p = 0.0001). Side-effects were reported with significantly higher frequency in patients receiving dihydralazine (60%) as compared to those receiving ketanserin (17%, p < 0.0001). Perinatal outcome was comparable, however, umbilical cord arterial pH values (mean +/- SD) were higher with ketanserin compared to dihydralazine (7.25 +/- 0.07 vs 7.23 +/- 0.09, p = 0.038). The incidence of placental abruption was higher in patients receiving dihydralazine (5.5%) versus those receiving ketanserin (0.6%, p = 0.014). CONCLUSION: Ketanserin appears to be a better option than dihydralazine for treatment of severe preeclampsia since fewer maternal complications and side-effects were observed in patients receiving ketanserin.

Lack of agreement between central venous pressure and pulmonary capillary wedge pressure in preeclampsia.

OBJECTIVE: To establish if agreement exists between central venous pressure (CVP) and pulmonary capillary wedge pressure (PCWP) measurements in severe hypertension in pregnancy as analyzed by tests of bias, precision, and 95% limits of agreement. METHODS: In a prospective study, CVP and PCWP data in 30 patients were collected by means of a pulmonary artery catheter from initiation of therapy until delivery. Patients with a diastolic blood pressure of more than 110 mm Hg were included. Correlation and agreement between CVP and PCWP before and after treatment were evaluated. RESULTS: The correlation coefficient (r) for CVP-PCWP data in 30 untreated patients was r = 0.64 (p = 0.0002) and for 256 pairs of posttreatment data, it was r = 0.53 (p < 0.0001). Linear regression and correlation for each individual patient in 29 patients with more than 3 measurements showed a significant correlation (p < 0.05) in 19 patients (66%). Correlation was poor (p > 0.05) in 10 patients (34%). The mean difference between PCWP and CVP was 3.5 +/- 2.6 mm Hg (limits of agreement: -1.6 to 8.7) in untreated patients. The mean difference between PCWP and CVP for 256 pairs of data derived posttreatment was 4.9 +/- 3.8 mm Hg (limits of agreement: -2.7 to 12. 5). CONCLUSION: Invasive measurements of CVP and PCWP were found to agree poorly. Until a reliable noninvasive method is available to measure left ventricular preload, PCWP is the measurement of choice when invasive hemodynamic monitoring is necessary in patients with severe preeclampsia.

Ketanserin versus dihydralazine in the management of severe early-onset preeclampsia: maternal outcome.

OBJECTIVE: An open, randomized, prospective, multicenter trial was conducted to compare the efficacy and safety of intravenous ketanserin, a selective serotonin 2 receptor blocker, with that of intravenous dihydralazine in the management of severe early-onset (<32 weeks' gestation) preeclampsia. End points of this study were blood pressure control and maternal outcome. STUDY DESIGN: Patients with a diastolic blood pressure >110 mm Hg were randomly assigned to receive either ketanserin (n = 22) or dihydralazine (n = 22) as initial therapy. Plasma volume expansion preceded antihypertensive treatment, which was administered according to a fixed schedule. RESULTS: The reductions in blood pressure with the 2 drugs were similar; however, adequate blood pressure control was reached significantly earlier with ketanserin (84 +/_ 63 vs 171 +/- 142 minutes, P = .017). Occurrence of maternal complications was significantly lower among patients who received ketanserin than among patients who received dihydralazine (n = 6 vs n = 18, P =.0007). A significant difference in favor of ketanserin was noted in daily fluid balance. CONCLUSION: Antihypertensive efficacies of ketanserin and dihydralazine were comparable, but significantly fewer maternal complications were noted among the patients receiving ketanserin. Ketanserin is an attractive alternative in the management of severe early-onset preeclampsia.