Does 17-α-hydroxyprogesterone caproate affect fetal biometry and birth weight in twin pregnancy?

OBJECTIVE: Increasingly, maternal administration of 17-α-hydroxyprogesterone caproate (17-OHPC) is utilized to prevent preterm birth, but the fetal safety of 17-OHPC is still a matter of concern. This study aimed to assess whether exposure to 17-OHPC during the second and third trimesters of pregnancy affects fetal biometry in twin gestations. METHODS: This study included a subset of women with a twin pregnancy who had been previously included in a randomized clinical trial comparing the effectiveness of 17-OHPC and placebo on neonatal outcomes and preterm birth rates in multiple pregnancy. In the present study, the individual growth patterns of femur length, head circumference and abdominal circumference were compared between fetuses of women who had been randomized to receive weekly injections of either 17-OHPC (n = 52) or placebo (n = 58) at between 16-20 and 36 weeks' gestation. RESULTS: The three biometric variables assessed developed similarly in fetuses in both the group exposed to 17-OHPC and the placebo group during the second half of pregnancy. Birth weight adjusted for parity and fetal sex was also comparable between groups. CONCLUSION: The use of 17-OHPC has no adverse effects on fetal biometry and birth weight in twins.

Carbetocin in comparison with oxytocin in several dosing regimens for the prevention of uterine atony after elective caesarean section in the Netherlands.

PURPOSE: The aim of the study was to compare the prophylactic effects of carbetocin with those of oxytocin for the prevention of uterine atony in patients undergoing elective caesarean section (CS) in the Netherlands. The primary endpoint was the need for additional uterotonic medication. METHODS: Each of the five participating Dutch hospitals treated 50-100 term patients with 100 µg of intravenous carbetocin on prescription. Each centre retrieved charts of 250 patients treated with oxytocin according to the hospital's policy for the prevention of uterine atony (oxytocin bolus 5 IU, bolus 10 IU or bolus 5 IU followed by 10 IU in 2 h). RESULTS: In the carbetocin group 462 subjects were included and in the oxytocin group 1,122. The proportion of subjects needing additional uterotonic treatment was 3.1 % (95 % CI 1.7-5.1 %) after carbetocin and 7.2 % (5.8-8.9 %) after oxytocin; relative risk 0.41 (0.19-0.85); p = 0.0110. Carbetocin was most effective compared with the oxytocin 5 IU bolus subgroup with less need for additional uterotonic medication (3.1 vs. 9.3 %, p = 0.0067) and blood transfusions (2.2 vs. 3.6 %, p = 0.0357). CONCLUSIONS: Compared with oxytocin, prophylaxis of uterine atony with carbetocin after an elective CS diminished the need for additional uterotonics by more than 50 %.

Effect of 17-alpha hydroxyprogesterone caproate on cervical length in twin pregnancies.

OBJECTIVES: Previous studies on singleton pregnancies have indicated that progestogens may reduce the rate of cervical shortening during pregnancy. The aim of this study was to investigate whether treatment with 17-alpha hydroxyprogesterone caproate (17-OHPC) has an effect on cervical shortening in twin pregnancies. METHODS: This was a secondary analysis of patients who had participated in a multicenter randomized clinical trial on the effectiveness of 17-OHPC in preventing preterm birth in multiple pregnancies (the AMPHIA-trial). We included all trial participants with a twin gestation who had undergone repeat cervical length measurements during pregnancy. We performed a separate analysis of women with repeat measurements in centers where this was standard protocol for multiple pregnancies. The rate of cervical shortening for both the 17-OHPC group and the placebo group was analyzed using a linear mixed model. RESULTS: Of the 671 patients who participated in the trial, 282 (42%) had a twin pregnancy and underwent two or more cervical length measurements. Of these women, 140 were monitored in centers where repeat measurements were standard protocol. We observed an overall reduction of cervical length from 44.3 mm at 14-18 weeks to 30.0 mm at 30-34 weeks' gestation. In the 17-OHPC group, cervical length decreased by 1.04 mm each gestational week, while this was 1.11 mm per week for the placebo group (P = 0.6). For the overall group, each 10% decrease in cervical length led to an increase in the risk of preterm birth (hazard ratio, 1.14; 95% CI, 1.08-1.21). CONCLUSION: In women with a twin pregnancy, there is progressive shortening of the cervix during pregnancy, regardless of 17-OHPC use.

Cervical length measurement for the prediction of preterm birth in multiple pregnancies: a systematic review and bivariate meta-analysis.

OBJECTIVES: To review the literature on cervical length as a predictor of preterm birth in asymptomatic women with a multiple pregnancy. METHODS: We searched MEDLINE, Embase and reference lists of included articles to identify all studies that reported on the accuracy of cervical length for predicting preterm birth in asymptomatic women with a multiple pregnancy. We scored study characteristics and study quality, and extracted data in order to construct two-by-two tables cross-classifying cervical length and preterm delivery. Meta-analysis using a bivariate model was performed. Summary receiver-operating characteristics (ROC) curves were generated for various test characteristics and outcome definitions. RESULTS: We found 21 studies reporting on 2757 women. There was a large variation in gestational age at measurement, cut-off point for cervical length and definition of preterm birth. The summary ROC curve indicated a good predictive capacity of short cervical length for preterm birth. Summary estimates of sensitivity and specificity for preterm birth before 34 weeks' gestation were 78% and 66%, respectively, for 35 mm, 41% and 87% for 30 mm, 36% and 94% for 25 mm and 30% and 94% for 20 mm. CONCLUSIONS: In women with a multiple pregnancy, second-trimester cervical length is a strong predictor of preterm birth. In the absence of effective preventive strategies, there is currently no place in clinical practice for cervical length measurement in this population. However, future studies should evaluate preventive interventions in women with multiple pregnancies and a short cervix, and cervical length should be measured in any trial studying preventive strategies in multiple pregnancies.

Prediction of fetal lung immaturity using gestational age, patient characteristics and fetal lung maturity tests: a probabilistic approach.

OBJECTIVES: The lecithin/sphingomyelin (L/S) ratio and the lamellar body count (LBC) can be used to predict respiratory distress syndrome (RDS). DESIGN: We performed a retrospective cohort study among consecutive women who underwent amniotic fluid sampling for the assessment of fetal lung maturity. Logistic regression was used to construct models for the prediction of RDS in three gestational age categories, with models based on clinical characteristics only, clinical characteristics and the LBC, and on clinical characteristics and L/S ratio. RESULTS: When amniotic fluid was collected <30 weeks, the specificity of the LBC was 30% and the sensitivity 100%. Addition of the L/S ratio increased the specifity to 60%, for a sensitivity of 100%. When amniocentesis was performed between 30 and 33 weeks, addition of the L/S ratio only marginally improved the performance of the LBC. CONCLUSIONS: At a gestational age <30 weeks, the L/S ratio has additional value over the LBC. Above 30 weeks of gestation, single use of the LBC seems sufficient.

Mediolateral episiotomy reduces the risk for anal sphincter injury during operative vaginal delivery.

OBJECTIVE: To determine the risk factors for anal sphincter injuries during operative vaginal delivery. SETTING AND DESIGN: A population-based observational study. POPULATION: All 21 254 women delivered with vacuum extraction and 7478 women delivered with forceps, derived from the previously validated Dutch National Obstetric Database from the years 1994 to 1995. METHODS: Anal sphincter injury was defined as any injury, partial or complete, of the anal sphincters. Risk factors were determined with multivariate logistic regression analysis. MAIN OUTCOME MEASURES: Individual obstetric factors, e.g. fetal birthweights, duration of second stage, etc. RESULTS: Anal sphincter injury occurred in 3.0% of vacuum extractions and in 4.7% of forceps deliveries. Primiparity, occipitoposterior position and fetal birthweight were associated with an increased risk for anal sphincter injury in both types of operative vaginal delivery, whereas duration of second stage was associated with an increased risk only in vacuum extractions. Mediolateral episiotomy protected significantly for anal sphincter damage in both vacuum extraction (OR 0.11, 95% CI 0.09-0.13) and forceps delivery (OR 0.08, 95% CI 0.07-0.11). The number of mediolateral episiotomies needed to prevent one sphincter injury in vacuum extractions was 12, whereas 5 mediolateral episiotomies could prevent one sphincter injury in forceps deliveries. CONCLUSIONS: Primiparity and occipitoposterior presentation are strong risk factors for the occurrence of anal sphincter injury during operative vaginal delivery. The highly significant protective effect of mediolateral episiotomies in both types of operative vaginal delivery warrants the conclusions that this type of episiotomy should be used routinely during these interventions to protect the anal sphincters.

Trends in obstetric interventions in the Dutch obstetrical care system in the period 1993-2002.

OBJECTIVE: To determine trends in induction of labour-, instrumental vaginal delivery- and caesarean section rates in the Netherlands in the period 1993-2002. STUDY DESIGN: Data derived from The Netherlands Perinatal Registry and Statistics Netherlands were used to calculate annual rates for induction of labour, instrumental vaginal delivery and caesarean section. Regarding caesarean section, rates were also calculated for different subgroups with respect to parity, presentation of the fetus, gestational age and multiple pregnancies. In the subgroup of women with a singleton fetus in vertex presentation between 37 and 42 weeks of gestation instrumental delivery rates were compared for women with induced labours and women in spontaneous labour. RESULTS: The overall CS rate rose from 8.1 to 13.6%. Proportionally the rise was greatest for breech presentation (+37.7%), multiple gestations (+12.7%) and women delivering between 24 and 28 weeks (+9.5%). However, in absolute numbers the rise was most impressive in the group of women with a singleton fetus in vertex presentation between 37 and 42 weeks of gestation. Rate of induction of labour and instrumental vaginal delivery remained constant (approximately 15% respectively 10% of all deliveries). In nulliparous term women with singletons in vertex presentation the CS rate increased with 8.0% to a rate of 20.7% when labour was induced versus an increase of 3.4% to a rate of 7.5% in spontaneous labour. CONCLUSION: In absolute numbers the rise in CS was most extensive in the group of women with a singleton fetus in vertex presentation between 37 and 42 weeks of gestation. Induction of labour rates and instrumental vaginal delivery rates remained constant during the past decade.

Acute activation of the endothelium results in increased levels of active von Willebrand factor in hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome.

BACKGROUND: HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome is a severe complication of pre-eclampsia in pregnancy, characterized by microvascular platelet thrombi. Activation of the endothelium is thought to play a key role in pre-eclampsia and HELLP syndrome. Activation of endothelial cells may lead to release of von Willebrand factor (VWF) multimers, which are highly reactive with platelets. Normally, newly released multimers are cleaved by ADAMTS13, resulting in less reactive derivatives. OBJECTIVE: We hypothesized that HELLP syndrome is characterized by increased amounts of active VWF compared with healthy pregnancy and pre-eclampsia, due to acute activation of endothelial cells. This might contribute to thrombocytopenia and thrombotic microangiopathy. METHODS: Active VWF and ADAMTS13 activity were measured in healthy pregnant volunteers (n = 9), patients with pre-eclampsia (n = 6) and patients with HELLP syndrome (n = 14) at similar gestational ages. To study the role of endothelial cell activation, the propeptide/mature VWF ratio was determined, and VWF released by cultured endothelial cells was analyzed. RESULTS: Active VWF levels were increased 2.1-fold in HELLP syndrome compared with healthy pregnant volunteers (P < 0.001) and 1.6-fold compared with patients with pre-eclampsia (P = 0.001). ADAMTS13 activity was moderately decreased in patients with HELLP syndrome compared with healthy pregnant volunteers (P < 0.004), but not compared with patients with pre-eclampsia. The propeptide/mature VWF ratio was increased 1.7-fold compared with healthy pregnant volunteers (P < 0.001) and 1.5-fold compared with patients with pre-eclampsia (P < 0.05). A significant correlation was found between this ratio and the activation factor of VWF (r = 0.68, P < 0.001). The amount of active VWF was increased 1.4-fold in medium of stimulated endothelial cells when compared with non-stimulated cells (P < 0.05). CONCLUSION: Acute endothelial cell activation in HELLP syndrome and decreased ADAMTS13 activity result in increased amounts of active VWF. This might explain the consumptive thrombocytopenia and thrombotic microangiopathy associated with HELLP syndrome. Inhibition of circulating active VWF could be a potential new approach in the treatment of patients with HELLP syndrome.

Psychosocial factors and mode of delivery.

Childbirth is a substantial physical and emotional endeavor. Because emergency Cesarean and instrumental vaginal delivery impose a greater mortality and physical and emotional morbidity on both the mother and the infant than normal vaginal delivery, it is important to identify factors that are associated with the risk of operative delivery. In previous investigations, some associations have been found, but the effect of psychosocial factors is not clear. In this study we examined several factors which could be associated with the risk for instrumental and surgical delivery. In addition to biomedical factors we included psychosocial factors such as depressive symptoms, quality of the relationship of the woman with her partner, personality, lifestyle and educational level. We assessed 354 healthy nulliparous pregnant women with a child in vertex presentation and spontaneous onset of term labor using validated questionnaires. We found that social support from the woman's partner in pregnancy, lack of depressive symptoms and specific personality traits are not protective against instrumentally assisted vaginal delivery or emergency Cesarean section. Predictive factors for operative delivery after spontaneous onset of labor are higher fetal weight, non-occiput anterior presentation and advanced gestational age, and foremost fetal distress during parturition.

[Pregnancy complications as a risk factor for metabolic and cardiovascular disease in later life]. / Zwangerschapscomplicaties als risicofactor voor metabole en cardiovasculaire aandoeningen op latere leeftijd.

In recent years several large epidemiological studies have been published that demonstrate that women who experience gestational diabetes, pregnancy-induced hypertension or pre-eclampsia have an increased risk of developing type-2 diabetes mellitus and cardiovascular disease. 15-50% of women who experience gestational diabetes develop type-2 diabetes mellitus; the risk is particularly high in those who require insulin therapy during pregnancy. - Chronic hypertension frequently develops years after a pregnancy complicated by pregnancy-induced hypertension, especially in women who have had pregnancy-induced hypertension in multiple pregnancies. Women who experience pre-eclampsia in the first 36 weeks of pregnancy or in multiple pregnancies have an increased risk of cardiovascular morbidity and mortality in later life. Therefore gestational diabetes, pregnancy-induced hypertension and pre-eclampsia provide an opportunity to identify individuals with an increased risk of type-2 diabetes mellitus and cardiovascular disease at an early age. This may create new perspectives on prevention.

The transplacental passage of prednisolone in pregnancies complicated by early-onset HELLP syndrome.

During pregnancy the placental 11beta-hydroxysteroid dehydrogenase 2 (11beta-HSD2) enzyme inactivates prednisolone by interconversion into prednisone, protecting the fetus from high levels of prednisolone. Recent reports suggest decreased placental 11beta-HSD2 activity in pregnancies complicated by preeclampsia. The purpose of our investigation was to study the transplacental passage of prednisolone in patients suffering from early preterm HELLP syndrome, a severe complication of preeclampsia. We examined the maternal and umbilical cord plasma concentration of prednisolone in nine women receiving 50 mg of prednisolone twice a day. Samples were obtained during caesarean section at a gestational age between 27 and 31 weeks. Mean fetal concentration was 10-fold lower as compared to maternal prednisolone concentration (mean+/-SD 52.8 nmol/L+/-27.0 vs. 477.5 nmol/L+/-300, p<0.01). A significant correlation was found between the last dose of prednisolone to delivery interval and the fetal prednisone concentration (Spearman's correlation coefficient r=-0.946, p<0.000). Our data demonstrate unimpaired placental 11beta-HSD2 activity in patients suffering from HELLP syndrome at early gestational age as shown by both a 10-fold lower fetal prednisolone concentration as compared to the mother and a strong correlation between the last dose of prednisolone to delivery interval and the fetal prednisone concentration. Prednisolone may therefore have less effect on the fetus than betamethasone or dexamethasone.

Corticosteroids, pregnancy, and HELLP syndrome: a review.

Corticosteroids are potent antiinflammatory and immunosuppressive drugs, which are used in the treatment of a wide range of medical disorders. During pregnancy, several corticosteroids are administered for maternal as well as fetal reasons. Prednisone and prednisolone show limited transplacental passage and are thus used for treatment of maternal disease. Dexamethasone and betamethasone, drugs that can easily cross the placenta, are more suitable for fetal indications. During the last decade, administration of corticosteroids was introduced in the treatment of hemolysis, elevated liver enzymes, and low platelets (HELLP syndrome), a severe form of preeclampsia unique to human pregnancy. Several randomized, controlled trials as well as other prospective and retrospective studies have been performed to investigate this beneficial effect of corticosteroids on biochemical measures and clinical signs. This review discusses the characteristics of corticosteroids in humans and details the use of corticosteroids during pregnancy. A review of literature on the effect of corticosteroids on HELLP syndrome is given and possible mechanisms of action are discussed.

[Breech presentation at term: elective caesarean section is the wrong choice as a standard treatment because of too high risks for the mother and her future children]. / Aterme stuitligging: onterechte keus voor de electieve keizersnede als standaardbehandeling vanwege te hoge risico's voor de moeder en haar volgende kinderen.

The altered attitude of the obstetrician with regard to term breech delivery after the first results of the Term breech trial in 2000 has led to an increase in elective caesarean section in the Netherlands from 25% in 1999 to 64% in 2004 and a decrease in emergency caesarean section for term breech delivery from 26% in 1999 to I8% in 2004. This increase of about 8500 elective caesarean sections in the last four years probably prevented 19 perinatal deaths. However, this rise in caesarean section also resulted in four maternal deaths that may have been avoidable. Furthermore, in the future, nine perinatal deaths as a result of the uterine scar and 140 women with potentially life-threatening complications from that uterine scar during their future pregnancies can be expected. Information to the patient should take into account not only the short-term benefits but also the higher long-term risks. Vaginal delivery following strict selection is now preferred.

Placental pathology in early onset pre-eclampsia and intra-uterine growth restriction in women with and without thrombophilia.

OBJECTIVE: The incidence of placental thrombotic lesions in early onset preeclampsia (PE) and/or intrauterine growth restriction (IUGR) were compared between women with and without thrombophilia or hyperhomocysteinemia. STUDY DESIGN: Matched case-control study. 183 women with a history of early onset PE and/or IUGR were tested for thrombophilia and hyperhomocysteinemia. From the 66 women with a thrombophilic factor the placental histological slides were available in 47 women. These were matched for maternal condition (PE and/or IUGR), gestational age at delivery, parity and maternal age, to 47 women with no thrombophilic factor. All slides were revised for lymphohistiocytic villitis, fetal thrombosis and fibrin depositions. RESULTS: There were no significant differences between the placentas of the matched groups with and without a thrombophilic factor. CONCLUSION: Placental thrombotic and inflammatory lesions associated with early onset PE and/or IUGR do not occur more often in women with compared to women without thrombophilia or hyperhomocysteinemia.

Placental superoxide is increased in pre-eclampsia.

One of the current hypotheses on the pathophysiology of pre-eclampsia (PE) states that the placenta secretes one or more cytotoxic factors resulting in maternal endothelial dysfunction. Among the candidate factors are the products of increased oxidative stress. Although there is circumstantial evidence of such an increase, direct evidence is still lacking. Electron paramagnetic spin trap resonance (EPR), the most direct method to detect free radicals in tissues, was used to measure superoxide levels in placentae from normal pregnancies (n=13) and pregnancies complicated by PE (n=10). The superoxide level was significantly increased in the placental tissue of pre-eclamptic women. Moreover, upon inhibition of Cu-Zn superoxide dismutase (SOD) activity the relative increase of the superoxide levels was significantly smaller in the placentae from the PE patients, implying decreased basal Cu-Zn SOD activity. These findings lend direct support to the hypothesis that oxidative stress in placental tissue is increased in PE.

Cardiac output in normal pregnancy: a critical review.

OBJECTIVE: To review the literature about the effect of normal pregnancy on cardiac output, with special attention to study design, measurement technique, position of the subject, and parity. DATA SOURCES: For studies from the period 1955-1987, we examined Cumulated Index Medicus (National Library of Medicine Cataloging in Publication. Chicago: American Medical Association). For studies from 1988 to May 1, 1994, we used Medline on Silver Platter (U.S. National Library of Medicine Silver Platter International, 1994). METHODS OF STUDY SELECTION: Thirty-three cross-sectional and 19 longitudinal studies on cardiac output measurement in normal pregnancy were retrieved and reviewed. Thirteen longitudinal studies were excluded from analysis because an unvalidated technique was used or because not all subjects were measured at each study interval. The six remaining studies of genuine longitudinal design with at least two measurements throughout pregnancy were used for the definitive analysis. The results of the cross-sectional studies were included only to demonstrate a trend. DATA EXTRACTION AND SYNTHESIS: By pooling data from cross-sectional studies, a tendency was shown toward a higher cardiac output in the second trimester compared with the first trimester, and a tendency toward lower cardiac output was found in the third trimester compared with the second trimester. After delivery, cardiac output was lower than at any time during pregnancy. Selected longitudinal studies showed that the rise in cardiac output occurred early in the first trimester, and a further rise occurred during the second trimester. During the third trimester, cardiac output rose, fell, or plateaued, irrespective of the method of measurement applied or conditions during measurement. CONCLUSIONS: Cardiac output during the third trimester was widely divergent among the studies and probably dependent on individual factors. The tendency to report cardiac output as averages negated these inter-individual differences.

Effects of antenatal corticosteroid administration on mortality and long-term morbidity in early preterm, growth-restricted infants.

OBJECTIVE: To evaluate the effect of antenatal corticosteroids on mortality, morbidity, and disability or handicap rate in early preterm, growth-restricted infants. METHODS: This case-control study in two tertiary care centers included all live-born singleton infants with growth-restriction due to placental insufficiency, who were delivered by cesarean because of cardiotocographic signs of fetal distress before the beginning of labor at a gestational age of 26-32 weeks during the years 1984-1991. Infants who had been treated antenatally with corticosteroids more than 24 hours and less than 7 days before birth were matched by birth weight, sex, and year of birth with infants whose mothers had been admitted more than 24 hours before delivery but were not treated antenatally with steroids. The main outcome measure was survival without disability or handicap at 2 years corrected age. A sample of 60 case-control pairs would give 81% power to demonstrate 50% increase of this outcome [odds ratio (OR) 3.0] by corticosteroid treatment. Behavior and physical growth were evaluated at school age by questionnaire. RESULTS: The study group and control group consisted of 62 infants each. Survival without disability or handicap at 2 years' corrected age was more frequent in the corticosteroid group [OR 3.2, confidence interval (CI) 1.1, 11.2]. In the long-term follow-up at school age there was a statistically significant negative effect on physical growth (OR 5.1, CI 1.4, 23.8), but no differences in behavior were detected. CONCLUSION: Benefits from antenatal corticosteroids for early preterm, growth-restricted infants appear to outweigh possible adverse effects.

A longitudinal study of maternal hemodynamics during normal pregnancy.

OBJECTIVE: To investigate the maternal hemodynamic changes that occur during normal pregnancy. METHODS: Serial hemodynamic investigations were performed throughout normal pregnancy by thoracic electrical bioimpedance monitoring in 50 healthy women. Analysis of variance with repeated measurements was used to evaluate the time course of a number of hemodynamic indies. RESULTS: The mean heart rate (+/- standard error [SE]) increased gradually from 87 +/- 2 beats per minute at 10-18 weeks' gestation to 92 +/- 1 beats per minute at 34-42 weeks' gestation. Mean arterial pressure decreased significantly after 14 weeks' gestation and increased significantly after 29 weeks' gestation. During the third trimester, mean cardiac output and mean stroke volume decreased, and mean systemic vascular resistance increased significantly. The course of cardiac output during the third trimester was not uniform in all women; it increased in nine and decreased in 41 women. A significantly higher mean cardiac output was found in nulliparous women compared with multiparous women (mean difference +/- SE 0.76 +/- 0.33 L/minute). The mean (+/- SE) cardiac output increased significantly from 6 (5.49 +/- 0.16 L/minute) to 12 weeks' postpartum (5.91 +/- 0.19 L/minute). CONCLUSION: Mean cardiac output and mean stroke volume decreased in late pregnancy. A significant difference in mean cardiac output was observed between nulliparous and multiparous women. Cardiac output usually, but not invariably, declined during the third trimester.

Emergency cerclage: a review.

The treatment of patients with cervical incompetence presenting with advanced cervical changes in the second trimester remains a challenge to every obstetrician. Cerclage operation may be the only hope for prolonging gestation until fetal viability is reached. A retrospective study on so-called emergency cervical cerclage in 20 patients with supposed cervical incompetence in the late second trimester is presented, together with a review of comparable studies published between 1980 and 1992. It is concluded that emergency cerclage can be of benefit, and that the pregnancy is saved in the majority of cases, although the incidence of complications, often due to infection, is high. Many patients require prolonged hospitalization or bed rest and few pregnancies reach full term. There is a particularly high rate of infectious complications and attention must be focused on preventing chorioamnionitis to improve the outcome of the procedure in the future.

Salivary cortisol levels and anxiety are not increased in women destined to develop preeclampsia.

OBJECTIVE: To compare salivary cortisol levels and maternal anxiety (general and pregnancy-specific) in the early and late second trimester of pregnancy between women who developed preeclampsia (PE) and women who remained normotensive. DESIGN: Nested case-referent study. In a prospectively studied cohort of 250 pregnant women, nine women developed PE in late pregnancy. These nine patients were matched and compared with nine controls. Diurnal cortisol levels were obtained by collecting saliva samples at 17-18 and 27-28 weeks gestation. Salivary cortisol levels were determined by radioimmunoassay. Maternal anxiety was determined by Spielberger's State-Trait Anxiety Inventory (STAI) and a pregnancy-specific stress questionnaire. RESULTS: For both patients and controls, a similar pattern of salivary cortisol excretion was observed. Salivary cortisol levels and anxiety scores (general and pregnancy-specific) did not differ significantly between patients and controls. CONCLUSIONS: Our findings do not lend support to a role for maternal anxiety or second trimester increases in circulating stress hormones in the pathogenesis of PE.