Josje Langenveld

Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial

BACKGROUND There is little evidence to guide the management of women with hypertensive disorders in late preterm pregnancy. We investigated the effect of immediate delivery versus expectant monitoring on maternal and neonatal outcomes in such women. METHODS We did an open-label, randomised controlled trial, in seven academic hospitals and 44 non-academic hospitals in the Netherlands. Women with non-severe hypertensive disorders of pregnancy between 34 and 37 weeks of gestation were randomly allocated to either induction of labour or caesarean section within 24 h (immediate delivery) or a strategy aimed at prolonging pregnancy until 37 weeks of gestation (expectant monitoring). The primary outcomes were a composite of adverse maternal outcomes (thromboembolic disease, pulmonary oedema, eclampsia, HELLP syndrome, placental abruption, or maternal death), and neonatal respiratory distress syndrome, both analysed by intention-to-treat. This study is registered with the Netherlands Trial Register (NTR1792). FINDINGS Between March 1, 2009, and Feb 21, 2013, 897 women were invited to participate, of whom 703 were enrolled and randomly assigned to immediate delivery (n=352) or expectant monitoring (n=351). The composite adverse maternal outcome occurred in four (1·1%) of 352 women allocated to immediate delivery versus 11 (3·1%) of 351 women allocated to expectant monitoring (relative risk [RR] 0·36, 95% CI 0·12-1·11; p=0·069). Respiratory distress syndrome was diagnosed in 20 (5·7%) of 352 neonates in the immediate delivery group versus six (1·7%) of 351 neonates in the expectant monitoring group (RR 3·3, 95% CI 1·4-8·2; p=0·005). No maternal or perinatal deaths occurred. INTERPRETATION For women with non-severe hypertensive disorders at 34-37 weeks of gestation, immediate delivery might reduce the already small risk of adverse maternal outcomes. However, it significantly increases the risk of neonatal respiratory distress syndrome, therefore, routine immediate delivery does not seem justified and a strategy of expectant monitoring until the clinical situation deteriorates can be considered. FUNDING ZonMw.

Tubal perforation by Essure: three different clinical presentations

OBJECTIVE To assess the convenience and safety of Essure sterilization in an outpatient setting and the use of ultrasound as diagnostic tool for verification of proper placement for the 3-month follow-up. DESIGN Prospective cohort study. SETTING Teaching hospital department of obstetrics and gynecology. PATIENT(S) Female patients with a request for permanent tubal sterilization. INTERVENTION(S) Essure sterilization. MAIN OUTCOME MEASURE(S) Bilateral tubal occlusion after Essure sterilization and complication rate. RESULT(S) A total of 149 patients were scheduled for Essure sterilization. Microinsert placement was attempted in 143 patients. Bilateral placement of the device was successful in 95% (95% confidence interval [CI] 92%-99%). Seven attempts were unsuccessful. The complication rate was 2% (n = 3), and all involved a perforation. These three cases are discussed in detail. Vaginal ultrasound was conclusive in 91.7% (95% CI 87%-96%); two perforations were not recognized on the ultrasound. CONCLUSION(S) Essure sterilization is a safe and reliable sterilization method in an outpatient setting. Perforation of the device is the most frequent complication. Vaginal ultrasound is reliable for verification after an uncomplicated procedure. When the procedure is difficult (e.g., higher resistance, more pain then average, more time or more than two devices needed), a hysterosalpingogram should be performed.

Neonatal outcome of pregnancies complicated by hypertensive disorders between 34 and 37 weeks of gestation : a 7 year retrospective analysis of a national registry

OBJECTIVE The objective of the study was to determine the neonatal morbidity in late preterm infants born from mothers with a hypertensive disorder. STUDY DESIGN Data were obtained from the national Perinatal Registry in The Netherlands on women who delivered between 34(+0) and 36(+6) weeks with gestational hypertension (n = 4316), preeclampsia (n = 1864), and normotensive controls (n = 20,749). RESULTS Children from mothers with preeclampsia had an increased risk for admission to the neonatal intensive care unit compared with children from normotensive mothers (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.8-2.2). A cesarean delivery and decreasing gestational age were independent risk factors for neonatal respiratory morbidity. Gestational hypertension or preeclampsia reduced the risk of respiratory distress syndrome compared with the control group (OR, 0.81; 95% CI, 0.64-1.0 and OR, 0.69; 95% CI, 0.49-0.96, respectively). CONCLUSION Neonatal morbidity in the late preterm period is considerable. Hypertensive disorders appear to protect for neonatal respiratory morbidity, but higher rates of cesarean section diminish this protective effect.

Recurrence of hypertensive disorders of pregnancy: an individual patient data metaanalysis.

OBJECTIVE We performed an individual participant data (IPD) metaanalysis to calculate the recurrence risk of hypertensive disorders of pregnancy (HDP) and recurrence of individual hypertensive syndromes. STUDY DESIGN We performed an electronic literature search for cohort studies that reported on women experiencing HDP and who had a subsequent pregnancy. The principal investigators were contacted and informed of our study; we requested their original study data. The data were merged to form one combined database. The results will be presented as percentages with 95% confidence interval (CI) and odds ratios with 95% CI. RESULTS Of 94 eligible cohort studies, we obtained IPD of 22 studies, including a total of 99,415 women. Pooled data of 64 studies that used published data (IPD where available) showed a recurrence rate of 18.1% (n=152,213; 95% CI, 17.9-18.3%). In the 22 studies that are included in our IPD, the recurrence rate of a HDP was 20.7% (95% CI, 20.4-20.9%). Recurrence manifested as preeclampsia in 13.8% of the studies (95% CI,13.6-14.1%), gestational hypertension in 8.6% of the studies (95% CI, 8.4-8.8%) and hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome in 0.2% of the studies (95% CI, 0.16-0.25%). The delivery of a small-for-gestational-age child accompanied the recurrent HDP in 3.4% of the studies (95% CI, 3.2-3.6%). Concomitant HELLP syndrome or delivery of a small-for-gestational-age child increased the risk of recurrence of HDP. Recurrence increased with decreasing gestational age at delivery in the index pregnancy. If the HDP recurred, in general it was milder, regarding maximum diastolic blood pressure, proteinuria, the use of oral antihypertensive and anticonvulsive medication, the delivery of a small-for-gestational-age child, premature delivery, and perinatal death. Normotensive women experienced chronic hypertension after pregnancy more often after experiencing recurrence (odds ratio, 3.7; 95% CI, 2.3-6.1). CONCLUSION Among women that experience hypertension in pregnancy, the recurrence rate in a next pregnancy is relatively low, and the course of disease is milder for most women with recurrent disease. These reassuring data should be used for shared decision-making in women who consider a new pregnancy after a pregnancy that was complicated by hypertension.

Recurrence risk and prediction of a delivery under 34 weeks of gestation after a history of a severe hypertensive disorder

Please cite this paper as: Langenveld J, Buttinger A, van der Post J, Wolf H, Mol B, Ganzevoort W. Recurrence risk and prediction of a delivery under 34 weeks of gestation after a history of a severe hypertensive disorder. BJOG 2011;118:589–595.

Economic analysis of use of pessary to prevent preterm birth in women with multiple pregnancy (ProTWIN trial)

To assess the cost‐effectiveness of a cervical pessary to prevent preterm delivery in women with a multiple pregnancy.

Prediction of recurrence of hypertensive disorders of pregnancy between 34 and 37 weeks of gestation: a retrospective cohort study

Please cite this paper as: van Oostwaard M, Langenveld J, Bijloo R, Wong K, Scholten I, Loix S, Hukkelhoven C, Vergouwe Y, Papatsonis D, Mol B, Ganzevoort W. Prediction of recurrence of hypertensive disorders of pregnancy between 34 and 37 weeks of gestation: a retrospective cohort study. BJOG 2012;119:840–847.

Prediction of recurrence of hypertensive disorders of pregnancy in the term period, a retrospective cohort study.

OBJECTIVES To assess the recurrence risk of term hypertensive disease of pregnancy and to determine which potential risk factors are predictive of recurrence. STUDY DESIGN We performed a retrospective cohort study in two secondary and one tertiary care hospitals in the Netherlands. We identified women with a hypertensive disorder in the index pregnancy and delivery after 37weeks of gestation between January 2000 and December 2002. Data were extracted from medical files and women were approached for additional information on subsequent pregnancies. Adverse outcome was defined as recurrence of a hypertensive disorder in the next subsequent pregnancy. MAIN OUTCOME MEASURES The absolute risk of recurrence and a prediction model containing demographic and clinical factors predictive of recurrence. RESULTS We identified 638 women for potential inclusion, of whom 503 could be contacted. Of these women, 312 (62%) had a subsequent pregnancy. Hypertensive disorders recurred in 120 (38%, 95% CI 33-44) women, of whom 15 (5%, 95% CI 3-7) delivered preterm. Women undergoing recurrence were more at risk to develop chronic hypertension after pregnancy (35% versus 16%, OR 2.8, 95% CI 1.5-5.3). Body mass index, non-White European origin, chronic hypertension, maximum diastolic blood pressure, no use of anticonvulsive medication and interpregnancy interval were predictors for recurrence. CONCLUSIONS Women with hypertensive disorders and term delivery have a substantial chance of recurrence, but a small risk of preterm delivery. A number of predictors for recurrence could be identified and women with a recurrence more often developed chronic hypertension.

In utero programming of adult vascular function in transgenic mice lacking low-density lipoprotein receptor

OBJECTIVE The objective of this study was to examine the role of maternal hypercholesterolemia in fetal programming of adult vascular function using transgenic mice lacking the low-density lipoprotein receptor (LDLR). STUDY DESIGN Homozygous LDLR knockout mice (B6.129S7-Ldlr(tm1Her)/J, LDLR(-/-KO)) and their wild-type controls (C57BL/6J, LDLR(+/+WT)) were cross-bred to produce 4 litter groups: LDLR(-/-KO), maternally derived heterozygous (LDLR(+/-Mat)), paternally derived heterozygous (LDLR(+/-Pat)) and LDLR(+/+WT). Female and male offspring were killed at 10-12 weeks of age, and carotid arteries were used for in vitro experiments. RESULTS The dose responses to phenylephrine were significantly higher in LDLR(-/-KO) and LDLR(+/-Mat) male offspring. The contractile responses to phenylephrine in female mice were significantly increased only in the LDLR(-/-KO) offspring. Maximal Ca(2+) contraction was higher in LDLR(-/-KO) male and female offspring. CONCLUSION Despite being genomically similar, heterozygous offspring that developed in a hypercholesterolemic maternal environment had abnormal vascular responses later in life compared with those that developed in a normal environment.

Surgical versus expectant management in women with an incomplete evacuation of the uterus after treatment with misoprostol for miscarriage: the MisoREST trial

BackgroundMedical treatment with misoprostol is a non-invasive and inexpensive treatment option in first trimester miscarriage. However, about 30% of women treated with misoprostol have incomplete evacuation of the uterus. Despite being relatively asymptomatic in most cases, this finding often leads to additional surgical treatment (curettage). A comparison of effectiveness and cost-effectiveness of surgical management versus expectant management is lacking in women with incomplete miscarriage after misoprostol.Methods/DesignThe proposed study is a multicentre randomized controlled trial that assesses the costs and effects of curettage versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage.Eligible women will be randomized, after informed consent, within 24 hours after identification of incomplete evacuation of the uterus by ultrasound scanning. Women are randomly allocated to surgical or expectant management. Curettage is performed within three days after randomization.Primary outcome is the sonographic finding of an empty uterus (maximal diameter of any contents of the uterine cavity < 10 millimeters) six weeks after study entry. Secondary outcomes are patients’ quality of life, surgical outcome parameters, the type and number of re-interventions during the first three months and pregnancy rates and outcome 12 months after study entry.DiscussionThis trial will provide evidence for the (cost) effectiveness of surgical versus expectant management in women with incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage.Trial registrationDutch Trial Register: NTR3110