Jim van Eyck

17α-hydroxyprogesterone caproate for the prevention of adverse neonatal outcome in multiple pregnancies: a randomized controlled trial.

OBJECTIVE: To estimate whether administration of 17&agr;-hydroxyprogesterone caproate can prevent neonatal morbidity in multiple pregnancies by reducing the preterm birth rate. METHODS: We conducted a multicenter, double-blind, placebo-controlled randomized trial in 55 obstetric clinics in the Netherlands. Women with a multiple pregnancy were randomized to weekly injections of either 250 mg 17&agr;-hydroxyprogesterone caproate or placebo, starting between 16 and 20 weeks of gestation and continuing until 36 weeks of gestation. The main outcome measure was adverse neonatal outcome. Secondary outcome measures were gestational age at delivery and delivery before 28, 32, and 37 weeks of gestation. RESULTS: We randomized 671 women. A composite measure of adverse neonatal outcome was present in 110 children (16%) born to mothers in the 17&agr;-hydroxyprogesterone caproate group, and in 80 children (12%) of mothers in the placebo group (relative risk [RR] 1.34; 95% confidence interval [CI] 0.95–1.89). The mean gestational age at delivery was 35.4 weeks for the 17&agr;-hydroxyprogesterone caproate group and 35.7 weeks for the placebo group (P=.32). Treatment with 17&agr;-hydroxyprogesterone caproate did not reduce the delivery rate before 28 weeks (6% in the 17&agr;-hydroxyprogesterone caproate group compared with 5% in the placebo group, RR 1.04; 95% CI 0.56–1.94), 32 weeks (14% compared with 10%, RR 1.37; 95% CI 0.91–2.05), or 37 weeks of gestation (55% compared with 50%, RR 1.11; 95% CI 0.97–1.28). CONCLUSION: 17&agr;-hydroxyprogesterone caproate does not prevent neonatal morbidity or preterm birth in multiple pregnancies. CLINICAL TRIAL REGISTRATION: ISRCTN Register, www.isrctn.org, ISRCTN40512715. LEVEL OF EVIDENCE: I

Effect of Maintenance Tocolysis With Nifedipine in Threatened Preterm Labor on Perinatal Outcomes A Randomized Controlled Trial

IMPORTANCE In threatened preterm labor, maintenance tocolysis with nifedipine, after an initial course of tocolysis and corticosteroids for 48 hours, may improve perinatal outcome. OBJECTIVE To determine whether maintenance tocolysis with nifedipine will reduce adverse perinatal outcomes due to premature birth. DESIGN, SETTING, AND PARTICIPANTS APOSTEL-II (Assessment of Perinatal Outcome with Sustained Tocolysis in Early Labor) is a double-blind, placebo-controlled trial performed in 11 perinatal units including all tertiary centers in The Netherlands. From June 2008 to February 2010, women with threatened preterm labor between 26 weeks (plus 0 days) and 32 weeks (plus 2 days) gestation, who had not delivered after 48 hours of tocolysis and a completed course of corticosteroids, were enrolled. Surviving infants were followed up until 6 months after birth (ended August 2010). INTERVENTION Randomization assigned 406 women to maintenance tocolysis with nifedipine orally (80 mg/d; n = 201) or placebo (n = 205) for 12 days. Assigned treatment was masked from investigators, participants, clinicians, and research nurses. MAIN OUTCOME MEASURES Primary outcome was a composite of adverse perinatal outcomes (perinatal death, chronic lung disease, neonatal sepsis, intraventricular hemorrhage >grade 2, periventricular leukomalacia >grade 1, or necrotizing enterocolitis). Analyses were completed on an intention-to-treat basis. RESULTS Mean (SD) gestational age at randomization was 29.2 (1.7) weeks for both groups. Adverse perinatal outcome was not significantly different between groups: 11.9% (24/201; 95% CI, 7.5%-16.4%) for nifedipine vs 13.7% (28/205; 95% CI, 9.0%-18.4%) for placebo (relative risk, 0.87; 95% CI, 0.53-1.45). CONCLUSIONS AND RELEVANCE In patients with threatened preterm labor, nifedipine-maintained tocolysis did not result in a statistically significant reduction in adverse perinatal outcomes when compared with placebo. Although the lower than anticipated rate of adverse perinatal outcomes in the control group indicates that a benefit of nifedipine cannot completely be excluded, its use for maintenance tocolysis does not appear beneficial at this time. TRIAL REGISTRATION trialregister.nl Identifier: NTR1336.

Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor

OBJECTIVE: To estimate the performance of combining cervical length measurement with fetal fibronectin testing in predicting delivery in women with symptoms of preterm labor. METHODS: We conducted a prospective nationwide cohort study in all 10 perinatal centers in The Netherlands. Women with symptoms of preterm labor between 24 and 34 weeks of gestation with intact membranes were included. In all women, qualitative fibronectin testing (0.050-microgram/mL cutoff) and cervical length measurement were performed. Logistic regression was used to predict spontaneous preterm delivery within 7 days after testing. A risk less than 5%, corresponding to the risk for women with a cervical length of at least 25 mm, was considered as low risk. RESULTS: Between December 2009 and August 2012, 714 women were enrolled. Fibronectin results and cervical length were available for 665 women, of whom 80 (12%) delivered within 7 days. Women with a cervical length of at least 30 mm or with a cervical length between 15 and 30 mm with a negative fibronectin result were at low risk (less than 5%) of spontaneous delivery within 7 days. Fibronectin testing in case of a cervical length between 15 and 30 mm additionally classified 103 women (15% of the cohort) as low risk and 36 women (5% of the cohort) as high risk. CONCLUSION: Cervical length measurement, combined with fetal fibronectin testing in case of a cervical length between 15 and 30 mm, improves identification of women with a low risk to deliver spontaneously within 7 days. LEVEL OF EVIDENCE: II

Delayed-interval delivery in twin and triplet pregnancies: 17 years of experience in 1 perinatal center

OBJECTIVE There are few prospective cohorts of delayed-interval delivery for twin and triplet pregnancies. Nonetheless, the procedure is an option to improve perinatal outcome. STUDY DESIGN A standard protocol was designed before candidates for delayed interval were managed by the 2 authors from 1991 to 2007. Perinatal as maternal outcomes were evaluated up to 1 year. RESULTS In 93 twin and 34 triplet pregnancies, the inclusion criteria were fulfilled; in 45 twin and 8 triplet pregnancies, there were contraindications to prolong pregnancy; and in 10 twin and 26 triplet pregnancies, asynchronous delivery was not possible because of immediate delivery of the remaining multiples. Thus, the procedure was performed in only 41% (38/93) of twin and 35% (12/34) of triplet pregnancies admitted with threatening early delivery. Among twin pregnancies, the mean delay was 19 (1-107) days. When the first delivery was less than 25 weeks, no first twin but 9 of 18 second twins (50%) survived (P < .001). Survival rate of first twins born beyond 25 weeks was 13 of 20 (65%) compared with 19 of 20 (95%) (P = .03) in corresponding second twins. In 7 of 12 triplet pregnancies with the first born less than 25 weeks, 2 of 14 remaining triplets survived after an interval of 118 days. Beyond 25 weeks, 3 of 5 first and 4 of 10 remaining triplets survived after intervals of 2-13 days (P = n.s.). Delay between second and third triplet was never longer than 2 days. Frequent maternal complications were chorioamnionitis (22%), postpartum hemorrhage, retained placenta (10%), and abruption (6%). CONCLUSION Our study provides data to assist physicians in the informed consent process when asynchronous delivery is considered and feasible.

Effects of rectally administered paracetamol on infants delivered by vacuum extraction.

OBJECTIVE To evaluate whether paracetamol (20 mg/kg rectally) relieves pain in infants delivered by vacuum extraction, and improves clinical condition. METHODS Prospective, randomised, double-blind, placebo-controlled study. Infants delivered by vacuum extraction were randomised either to the study group (n=61) and given paracetamol or to the control group (n=61) receiving placebo. Pain assessment was performed by a validated pain score and by scoring the clinical condition. Both scores and clinical symptoms in these groups were compared with symptoms in a reference group (n=66) with uncomplicated pregnancy and delivery in vertex position without vacuum extraction. RESULTS Pain score did not differ between groups; clinical condition in the study group improved only after the first dose. There was a significant difference (P<0.05) in objective clinical symptoms in the vacuum extraction groups, compared to the reference group. CONCLUSION One dose of paracetamol given to neonates delivered by vacuum extraction significantly improved their clinical condition, but did not result in a significant change in objective pain scores. Subsequent doses of paracetamol did not show any effect on the clinical symptoms or appearance of the neonates studied.

Persistent abnormalities in plasma volume and renal hemodynamics in patients with a history of preeclampsia.

OBJECTIVE The objective was to test the hypothesis that women with a recent history of preeclampsia have abnormalities in renal hemodynamics and volume status. STUDY DESIGN We studied a group of 26 primiparous women with history of preeclampsia and a group of 12 parous women with a history of uneventful pregnancies (control group). At least 4 months post partum we compared the following variables between these groups: effective renal plasma flow, glomerular filtration rate, plasma volume, plasma concentration of active renin, plasma concentration of angiotensin II, plasma concentration of aldosterone, and plasma concentration of atrial natriuretic peptide. RESULTS Both plasma volume and plasma concentration of atrial natriuretic peptide were lower in the formerly preeclamptic group. Compared with the control subjects, the formerly preeclamptic group also had a lower effective renal plasma flow, a higher filtration fraction, and a higher renal vascular resistance. Intergroup differences in plasma concentration of active renin, plasma concentration of angiotensin II and plasma concentration of aldosterone were small and inconsistent. CONCLUSIONS Women with history of preeclampsia are relatively hypovolemic and tend to have lower effective renal plasma flow and higher renal vascular resistance and filtration fraction than do control subjects. These findings support the hypothesis that otherwise healthy women with a history of preeclampsia show abnormalities in their volume status and renal hemodynamics, irrespective of their blood pressure.

Cost-effectiveness of fibronectin testing in a triage in women with threatened preterm labor : alleviation of pregnancy outcome by suspending tocolysis in early labor (APOSTEL-I trial)

BackgroundAt present, women with threatened preterm labor before 32 weeks of gestation are, after transfer to a perinatal center, treated with tocolytics and corticosteroids. Many of these women are treated unnecessarily. Fibronectin is an accurate predictor for the occurrence of preterm birth among women with threatened preterm labor. We will assess whether triage of these women with fibronectin testing, cervical length or their combination is cost-effective.Methods/DesignWe will investigate a prospective cohort of women referred to a perinatal centre for spontaneous threatened preterm labor between 24 and 34 weeks with intact membranes. All women will be tested for fibronectin and cervical length. Women with a cervical length <10 mm and women with a cervical length between 10-30 mm in combination with a positive fibronectin test will be treated with tocolytics according to local protocol. Women with a cervical length between 10-30 mm in combination with a negative fibronectin test will be randomised between treatment with nifedipine (intervention) and placebo (control) for 48 hours. Women with a cervical length > 30 mm will be managed according to local protocol. Corticosteroids may be given to all women at the discretion of the attending physician. Primary outcome measure will be delivery within 7 days. Secondary outcome measures will be neonatal morbidity and mortality, complications of tocolytics, costs and health related quality of life. The analysis will be according to the intention to treat principle. We anticipate the probability on preterm birth within 7 days in the group of women with a negative fibronectine test to be 5%. Two groups of 110 women will be needed to assure that in case of non-inferiority the difference in the proportion of preterm deliveries < 7 days will be within a prespecified boundary of 7.5% (one sided test, β 0.2, α 0.05). Data obtained from women with a positive and negative fibronectin tests in both the cohort study and the trial will be integrated in a cost-effectiveness analysis that will assess economic consequences of the use of fibronectin.DiscussionThis study will provide evidence for the use of fibronectin testing as safe and cost-effective method in a triage for threatened preterm labor.Trial registrationNederlands Trial Register (NTR) number 1857, http://www.trialregister.nl.

Pessaries in multiple pregnancy as a prevention of preterm birth: the ProTwin Trial.

BackgroundMultiple pregnancies are at high risk for preterm birth, and therefore an important cause of infant mortality and morbidity. A pessary is a simple and potentially effective measure for the prevention of preterm birth. Small studies have indicated its effectiveness, but large studies with sufficient power on the subject are lacking. Despite this lack of evidence, the treatment is at present applied by some gynaecologists in The Netherlands.Methods/DesignWe aim to investigate the hypothesis that prophylactic use of a cervical pessary will be effective in the prevention of preterm delivery and the neonatal mortality and morbidity resulting from preterm delivery in multiple pregnancy. We will evaluate the costs and effects of this intervention. At study entry, cervical length will be measured. Eligible women will be randomly allocated to receive either a cervical pessary or no intervention. The cervical pessary will be placed in situ at 16 to 20 weeks, and will stay in situ up to 36 weeks gestation or until delivery, whatever comes first.The primary outcome is composite bad neonatal condition (perinatal death or severe morbidity). Secondary outcome measures are time to delivery, preterm birth rate before 32 and 37 weeks, days of admission in neonatal intensive care unit, maternal morbidity, maternal admission days for preterm labour and costs. We need to include 660 women to indicate a reduction in bad neonatal outcome from 7.2% without to 3.9% with a cervical pessary, using a two-sided test with an alpha of 0.05 and a power of 0.80.DiscussionThis trial will provide evidence on whether a cervical pessary will decrease the incidence of early preterm birth and its concomitant bad neonatal outcome in multiple pregnancies.Trial registrationCurrent Controlled Trials: NTR 1858

Ketanserin for the treatment of preeclampsia.

Abstract 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.

Liver rupture postpartum associated with preeclampsia and HELLP syndrome.

Liver rupture is a rare perinatal complication with high maternal mortality. In a multiparous woman with preeclampsia and Hemolysis, Elevated Liver enzymes, and Low Platelet count (HELLP) syndrome, liver rupture was suspected 10 h after a cesarean section. Laparotomy revealed liver rupture which was treated by perihepatic packing. Eventually, the mother was discharged with her baby 88 days after admission. Clinical symptoms, maternal hemodynamics by Swan-Ganz monitoring, and laboratory findings were not predictive until the emergency situation and the consecutive complications required multidisciplinary management.