Jérôme Cornette

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

Uteroplacental Blood Flow, Cardiac Function, and Pregnancy Outcome in Women With Congenital Heart Disease

Background— Pregnant women with congenital heart disease (CHD) are susceptible to cardiovascular, obstetric, and offspring complications. In women with CHD, cardiac dysfunction may compromise uteroplacental flow and contribute to the increased incidence of obstetric and offspring events. Methods and Results— We performed a prospective multicenter cohort study of pregnant women with CHD and healthy pregnant women. We compared clinical, laboratory, echocardiographic, and uteroplacental Doppler flow (UDF) parameters at 20 and 32 weeks gestation, and pregnancy outcome. We related cardiovascular parameters to UDF parameters and pregnancy outcome in women with CHD. We included 209 women with CHD and 70 healthy women. Cardiovascular parameters (N-terminal pro-B-type natriuretic peptide, left and right ventricular function) differed between both groups. UDF parameters were impaired in CHD women (umbilical artery pulsatility and resistance index at 32 weeks in CHD versus healthy women, P=0.0085 and P=0.017). The following cardiovascular parameters prepregnancy and at 20 weeks gestation were associated with UDF (umbilical artery resistance index) at 32 weeks at multivariable analysis: (1) right ventricular function (tricuspid annular plane systolic excursion) (P=0.002), (2) high N-terminal pro-B-type natriuretic peptide (P=0.085), (3) systemic (P=0.001), and (4) pulmonary (P=0.045) atrioventricular valve regurgitation. Women with CHD had more obstetric (58.9% versus 32.9%, P<0.0001) and offspring events (35.4% versus 18.6%, P=0.008) than healthy women. Impaired UDF was associated with adverse obstetric and offspring outcome. Conclusions— UDF parameters are abnormal in pregnant women with CHD. Cardiovascular function is associated with an abnormal pattern of UDF. Compromised UDF may be a key factor in the high incidence of offspring and obstetric complications in this population.

Pregnancy and delivery in cardiac disease

Although its prevalence is relatively low in pregnant women, heart disease is the most important cause of maternal mortality. Problems may arise due to hemodynamic burden and the hypercoagulable state of pregnancy. Heart disease may be congenital or acquired. In developed countries, the former composes the biggest part of women with heart disease. Patients with unrepaired lesions, cyanotic lesions, diminished systemic ventricular function, complex congenital heart disease, left ventricular outflow tract obstruction, pulmonary hypertension, or mechanical valves are at highest risk of developing complications during pregnancy. All patients with known cardiac disease should preferably be counseled before conception. Pre-pregnancy evaluation should include risk assessment for the mother and fetus, including medication use and information on heredity of the cardiac lesion. Management of pregnancy and delivery should be planned accordingly on individual bases. The types of complications are related to the cardiac diagnosis, with arrhythmias and heart failure being most common. Treatment options should be discussed with the future parents, as they may affect both mother and child. In general, the preferred route of delivery is vaginal. The optimal care for pregnant women with heart disease requires multidisciplinary involvement and is best concentrated in tertiary centers.

Quantitative cardiovascular magnetic resonance in pregnant women: cross-sectional analysis of physiological parameters throughout pregnancy and the impact of the supine position.

BackgroundThere are physiological reasons for the effects of positioning on hemodynamic variables and cardiac dimensions related to altered intra-abdominal and intra-thoracic pressures. This problem is especially evident in pregnant women due to the additional aorto-caval compression by the enlarged uterus. The purpose of this study was to investigate the effect of postural changes on cardiac dimensions and function during mid and late pregnancy using cardiovascular magnetic resonance (CMR).MethodsHealthy non-pregnant women, pregnant women at 20th week of gestation and at 32nd week of gestation without history of cardiac disease were recruited to the study and underwent CMR in supine and left lateral positions. Cardiac hemodynamic parameters and dimensions were measured and compared between both positions.ResultsFive non-pregnant women, 6 healthy pregnant women at mid pregnancy and 8 healthy pregnant women at late pregnancy were enrolled in the study. In the group of non-pregnant women left ventricular (LV) cardiac output (CO) significantly decreased by 9% (p = 0.043) and right ventricular (RV) end-diastolic volume (EDV) significantly increased by 5% (p = 0.043) from the supine to the left lateral position. During mid pregnancy LV ejection fraction (EF), stroke volume (SV), left atrium lateral diameter and left atrial supero-inferior diameter increased significantly from the supine position to the left lateral position: 8%, 27%, 5% and 11%, respectively (p < 0.05). RV EDV, SV and right atrium supero-inferior diameter significantly increased from the supine to the left lateral position: 25%, 31% and 13% (p < 0.05), respectively. During late pregnancy a significant increment of LV EF, EDV, SV and CO was observed in the left lateral position: 11%, 21%, 35% and 24% (p < 0.05), respectively. Left atrial diameters were significantly larger in the left lateral position compared to the supine position (p < 0.05). RV CO was significantly increased in the left lateral position compared to the supine position (p < 0.05).ConclusionsDuring pregnancy positional changes affect significantly cardiac hemodynamic parameters and dimensions. Pregnant women who need serial studies by CMR should be imaged in a consistent position. From as early as 20 weeks the left lateral position should be preferred on the supine position because it positively affects venous return, SV and CO.

Pregnancy Outcomes in Women With Aortic Valve Substitutes

Young women who require aortic valve replacement need information on the potential cardiac and obstetric complications of pregnancy for the different valve substitutes available. We, therefore, assessed the pregnancy outcomes in women who had received an autograft, homograft, or mechanical valve in the aortic position. Women who were pregnant after surviving aortic valve replacement at our institution from 1987 to 2011 were included. Information on cardiac status and pregnancy outcome was obtained through the hospital medical records and by an extensive patient questionnaire. A total of 40 women experienced 67 pregnancies, of which 55 (82%) were completed pregnancies, 6 (9%) were miscarriages, and 6 (9%) were terminated. Of the 40 women, 18 (45%) had a pulmonary autograft, 13 (32%) a homograft, and 9 (23%) a mechanical valve. The mean age at the first pregnancy was 30.0 ± 5.7 years. No maternal mortality but 1 fetal death (1.8%) and 1 neonatal death (1.8%) occurred. Maternal cardiac complications developed in 13% and obstetric complications in 38% of the completed pregnancies. Heart failure (9%), arrhythmias (7%), hypertension-related disorders (7%), preterm delivery (24%), and small-for-gestational-age infants (15%) were most often encountered. Mechanical valve recipients had the greatest incidence of both cardiac and obstetric complications. In conclusion, pregnancy-associated complications after aortic valve replacement were common, and human tissue valves should be considered in the discussion for the optimal aortic valve substitute in a young woman. However, careful obstetric monitoring is mandatory.

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.

Contraception and Cardiovascular Disease

Contraceptive counselling should begin early in females with heart disease, preferably directly after the start of menstruation. In coming to a decision about the method of contraception, the following issues should be considered: (i) the risk of pregnancy for the mother and the consequences of an unplanned pregnancy; (ii) the risks of the contraceptive method; (iii) failure rates; (iv) the non-contraceptive benefits; (v) the availability; (vi) the individuals preferences; (vii) protection against infection; and (viii) costs. In some women with heart disease, the issues may be complex and require the input of both a cardiologist and an obstetrician (or other feto-maternal expert) to identify the optimal approach. No studies have been performed in women with heart disease to investigate the relative risks and benefits of different contraceptive methods.

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

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.

Uterine artery pseudoaneurysm requiring embolization during pregnancy.

BACKGROUND: Uterine artery pseudoaneurysm has a pathognomonic ultrasound appearance. Its occurrence in pregnancy is life-threatening for both mother and fetus. We present an illustrative case and discuss management with selective uterine artery embolization during pregnancy. CASE: A 37-year-old pregnant woman presented with profuse painless vaginal blood loss at a gestational age of 27 weeks. Ultrasonography and magnetic resonance imaging indicated a left-sided uterine artery pseudoaneurysm. Selective embolization of the pseudoaneurysm was performed. Blood loss ceased allowing the pregnancy to continue until term. CONCLUSION: Endovascular embolization is a feasible therapeutic option for a uterine artery pseudoaneurysm during pregnancy without compromising fetoplacental perfusion.