Publications by authors named "Jérôme M J Cornette"

19 Publications

  • Page 1 of 1

Cardiometabolic Profiles in Women with a History of Hypertensive and Normotensive Fetal Growth Restriction.

J Womens Health (Larchmt) 2021 Sep 14. Epub 2021 Sep 14.

Department of Obstetrics and Gynecology, Erasmus University Medical Center, Rotterdam, the Netherlands.

The majority of evidence on associations between pregnancy complications and future maternal disease focuses on hypertensive (Ht) complications. We hypothesize that impaired cardiometabolic health after pregnancies complicated by severe fetal growth restriction (FGR) is independent of the co-occurrence of hypertension. In a prospective cohort of women with a pregnancy complicated by early FGR (delivery <34 weeks gestation), with or without concomitant hypertension, cardiometabolic risk factors were assessed after delivery. A population-based reference cohort was used for comparison, and analyses were adjusted for age, current body mass index (BMI), smoking habits, and hormonal contraceptive use. Median time from delivery to assessment was 4 months in both the Ht ( = 115) and normotensive (Nt) ( = 42) FGR groups. Compared with the reference group ( = 380), in both FGR groups lipid profile and glucose homeostasis at assessment were unfavorable. Women with Ht-FGR had the least favorable cardiometabolic profile, with higher prevalence ratios (PRs) for diastolic blood pressure >85 mmHg (PR 4.0, 95% confidence interval [CI] 2.1-6.7), fasting glucose levels >5.6 mmol/L (PR 2.9, 95% CI 1.4-5.6), and total cholesterol levels >6.21 mmol/L (PR 4.5, 95% CI 1.9-8.8), compared with the reference group. Women with Nt-FGR more often had a BMI >30 kg/m (PR 2.5, 95% CI 1.2-4.7) and high-density lipoprotein-cholesterol levels <1.29 mmol/L (PR 2.4, 95% CI 1.4-3.5), compared with the reference group. Women with a history of FGR showed unfavorable short-term cardiometabolic profiles in comparison with a reference group, independent of the co-occurrence of hypertension. Therefore, women with a history of FGR may benefit from cardiovascular risk factor assessment and subsequent risk reduction strategies.
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http://dx.doi.org/10.1089/jwh.2021.0079DOI Listing
September 2021

Low prevalence of anti-SSA (anti-Ro) and anti-SSB (anti-La) autoantibodies in female patients with rheumatoid arthritis with a wish to conceive.

RMD Open 2021 07;7(2)

Rheumatology, Erasmus Medical Center, Rotterdam, The Netherlands.

Objectives: Guidelines advise to test for anti-Sjögren's-syndrome-related antigen A (anti-SSA) and anti-Sjögren's-syndrome-related antigen B (anti-SSB) antibodies in all patients with rheumatoid arthritis (RA) who wish to conceive. Our objective was to determine the prevalence and titres of anti-SSA and anti-SSB autoantibodies in patients with RA with a wish to conceive or pregnant.

Methods: Patients were derived from two large cohorts on RA and pregnancy (PARA cohort and PreCARA cohort). In addition, to determine the clinical relevance of searching for anti-SSA and anti-SSB in patients with RA, we studied the prevalence of the maternal diagnosis of RA in the French national registry of neonatal lupus syndrome (NLS) and congenital heart block (CHB).

Results: 26 out of 647 patients with RA had detectable anti-SSA and/or anti-SSB. Anti-SSA was detected in 25 out of 647 patients (3.9%) (Ro-52, n=17; Ro-60, n=19), anti-SSB in 7 out of 647 (1.1%). Thirteen women had a titre of >240 units/mL of anti-SSA antibodies. The prevalence of anti-SSA and/or anti-SSB was higher in rheumatoid factor (RF)-positive patients compared with RF-negative patients (5.1% vs 1.6%, p=0.04). No cases of CHB and/or NLS in the offspring were observed. In the French national register, the prevalence of RA in mothers with SSA related CHB was 1.5%.

Conclusion: Anti-SSA and anti-SSB have a low prevalence in patients with RA who wish to conceive. Especially for RF-negative patients, the current advise to test for anti-SSA and anti-SSB should be reconsidered.
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http://dx.doi.org/10.1136/rmdopen-2021-001727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268898PMC
July 2021

Women of reproductive age in a tertiary intensive care unit: indications, outcome and the impact of pregnancy-a retrospective cohort study.

BMC Womens Health 2021 06 19;21(1):248. Epub 2021 Jun 19.

Department of Obstetrics and Gynecology, Erasmus MC - Sophia Children's Hospital, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background: To evaluate the indications for admission and mortality rates of women of reproductive age admitted to a tertiary Intensive Care Unit (ICU) and to compare the outcomes of obstetric and non-obstetric admissions.

Methods: A retrospective cohort study was performed, including all women aged 17-41 years admitted to a level 3 ICU in the Netherlands, between January 1, 2000 and January 1, 2016. Primary outcome was indication for admission and mortality. Mortality, length of stay (LOS), need for mechanical ventilation and APACHE II score were compared between obstetric and non-obstetric admissions. The obstetric group was further analyzed for maternal and perinatal outcomes.

Results: 3461 women (median age 32 years) were included, with an overall mortality rate of 13.3%. The obstetric group consisted of 265 women (7.7%). The non-obstetric group (n = 3196) was admitted most often for cardiovascular disease (19.6%), followed by oncologic disease (15%). Mortality was the highest in women with oncologic disease (23.9%). The obstetric group had lower mortality compared to the non-obstetric group (4.9% vs. 14%, p < 0.001), despite higher APACHE II score (14 vs. 11, p < 0.001) and a higher ventilation rate (47.9% vs. 39%, p = 0.004). Major surgical or endovascular interventions, besides caesarean section, were performed in 46% of the obstetric group. Perinatal death occurred in 17.2% and of the surviving infants, 63.2% were born preterm and 45.1% required Neonatal Intensive Care Unit admission.

Conclusions: Cardiovascular disease is the most important indication for admission and oncologic disease is associated with highest mortality in women of reproductive age. Obstetric patients constitute a small percentage of all ICU admissions in a tertiary ICU center. They have lower mortality rates than non-obstetric young female patients, despite a more severe initial presentation. Nevertheless lasting maternal morbidity and perinatal mortality and morbidity is frequent.
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http://dx.doi.org/10.1186/s12905-021-01396-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214372PMC
June 2021

The physiological effect of early pregnancy on a woman's response to a submaximal cardiopulmonary exercise test.

Physiol Rep 2020 11;8(21):e14624

Department of Obstetrics and Gynecology, Erasmus MC, University Medical Centre, Rotterdam, The Netherlands.

Given all its systemic adaptive requirements, pregnancy shares several features with physical exercise. In this pilot study, we aimed to assess the physiological response to submaximal cardiopulmonary exercise testing (CPET) in early pregnancy. In 20 healthy, pregnant women (<13 weeks gestation) and 20 healthy, non-pregnant women, we performed a CPET with stationary cycling during a RAMP protocol until 70% of the estimated maximum heart rate (HR) of each participant. Hemodynamic and respiratory parameters were non-invasively monitored by impedance cardiography (PhysioFlow ) and a breath-by-breath analyzer (Oxycon ). To compare both groups, we used linear regression analysis, adjusted for age. We observed a similar response of stroke volume, cardiac output (CO) and HR to stationary cycling in pregnant and non-pregnant women, but a slightly lower 1-min recovery rate of CO (-3.9 [-5.5;-2.3] vs. -6.6 [-8.2;-5.1] L min  min ; p = .058) and HR (-38 [-47; -28] vs. -53 [-62; -44] bpm/min; p = .065) in pregnant women. We also observed a larger increase in ventilation before the ventilatory threshold (+6.2 [5.4; 7.0] vs. +3.2 [2.4; 3.9] L min  min ; p < .001), lower P CO values at the ventilatory threshold (33 [31; 34] vs. 36 [34; 38] mmHg; p = .042) and a larger increase of breathing frequency after the ventilatory threshold (+4.6 [2.8; 6.4] vs. +0.6 [-1.1; 2.3] breaths min  min ; p = .015) in pregnant women. In conclusion, we observed a slower hemodynamic recovery and an increased ventilatory response to exercise in early pregnancy.
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http://dx.doi.org/10.14814/phy2.14624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7666775PMC
November 2020

Study protocol for a prospective cohort study to investigate Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome: the HAPPO study.

BMJ Open 2019 11 10;9(11):e033083. Epub 2019 Nov 10.

Department of Obstetrics and Gynecology, Erasmus MC, Rotterdam, The Netherlands

Introduction: The importance of cardiovascular health in relation to pregnancy outcome is increasingly acknowledged. Women who develop certain pregnancy complications, in particular preeclampsia, are at higher risk for future cardiovascular disease. Independent of its outcome, pregnancy requires a substantial adaptive response of the maternal cardiovascular system. In the Hemodynamic Adaptation to Pregnancy and Placenta-related Outcome (HAPPO) study, we aim to examine longitudinal maternal haemodynamic adaptation to pregnancy from the preconception period onwards. We hypothesise that women who will develop adverse pregnancy outcomes have impaired cardiovascular health before conception, leading to haemodynamic maladaptation to pregnancy and diminished uteroplacental vascular development.

Methods And Analysis: In this prospective cohort study embedded in the Rotterdam periconception cohort, 200 women with a history of placenta-related pregnancy complications (high-risk group) and 100 women with an uncomplicated obstetric history (low-risk group) will be included. At five moments (preconception, first, second and third trimester and postdelivery), women will undergo an extensive examination of the macrocirculatory and microcirculatory system and uteroplacental vascular development. The main outcome measures are differences in maternal haemodynamic adaptation to pregnancy between women with and without placenta-related pregnancy complications. In a multivariate linear mixed model, the relationship between maternal haemodynamic adaptive parameters, (utero)placental vascularisation indices and clinical outcomes (occurrence of pregnancy complications, embryonic and fetal growth trajectories, miscarriage rate, gestational age at delivery, birth weight) will be studied. Subgroup analysis will be performed to study baseline and trajectory differences between high-risk and low-risk women, independent of subsequent pregnancy outcome.

Ethics And Dissemination: This study protocol was approved by the Medical Ethics Committee of the Erasmus MC, Rotterdam, the Netherlands (MEC 2018-150). Results will be disseminated to the medical community by publications in peer-reviewed journals and presentations at scientific congresses. Also, patient associations will be informed and the public will be informed by dissemination through (social) media.

Trial Registration Number: NL7394 (www.trialregister.nl).
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http://dx.doi.org/10.1136/bmjopen-2019-033083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858161PMC
November 2019

Influence of pregnancy on long-term durability of allografts in right ventricular outflow tract.

J Thorac Cardiovasc Surg 2020 04 4;159(4):1508-1516.e1. Epub 2019 Oct 4.

Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address:

Background: There is very limited published evidence about the influence of pregnancy on allograft durability in right ventricular outflow tract position. We present the first study using mixed and joint modeling.

Methods: This retrospective study compared clinical and valve related outcomes of all consecutive female hospital survivors in their fertile life phase (18-50 years) based on pregnancy. Serial echocardiographic measurements of pulmonary gradient and regurgitation were analyzed for their association with valve replacement using joint models for longitudinal and time-to-event data. Occurrence of first pregnancy was included as a time-dependent intermediate event in both the longitudinal and survival analyses of the joint model to assess its impact on the hemodynamic and clinical outcome.

Results: In total, 196 consecutive women in their fertile life-phase with an allograft were included. Complete information of 176 (90%) allografts in 165 women was available, including 1395 echocardiograms. Of these women, 51 (30.9%) women had 84 completed pregnancies at an average age of 29.1 ± 3.9 (SD) years; 8.1 ± 6.1 years since allograft implantation. Tetralogy of Fallot was the most common diagnosis in both groups. After a mean follow-up of 15.2 years (range 0.1-30), 7 (13.7%) parous women underwent valve replacement versus 20 (17.5%) nulliparous women. During this follow-up, the mean allograft gradient in parous (24.2 mm Hg) and nulliparous (21.0 mm Hg) women was comparable (P = .225). A 1-mm Hg increase in pulmonary gradient increased the instantaneous risk of pulmonary valve replacement (PVR) by a ratio of 1.051 (P < .001), regardless of pregnancy. Similarly, development of moderate or severe regurgitation increased the risk of PVR (P = .038), regardless of pregnancy. Pregnancy was not associated with a change in the allograft gradient (P = .258), regurgitation grade (P = .774), or hazard of PVR (P = .796) during follow-up.

Conclusions: Pregnancy is not associated with impaired allograft durability in women with good cardiac health.
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http://dx.doi.org/10.1016/j.jtcvs.2019.08.083DOI Listing
April 2020

Outcomes of Pregnancy After Right Ventricular Outflow Tract Reconstruction With an Allograft Conduit.

J Am Coll Cardiol 2018 06;71(23):2656-2665

Department of Cardiothoracic Surgery, Erasmus University Medical Center, Rotterdam, the Netherlands. Electronic address:

Background: There is no published evidence on pregnancy after right ventricular outflow tract (RVOT) reconstruction with an allograft.

Objectives: The aim of this study was to describe pregnancy outcomes in women with allografts in the RVOT position.

Methods: A retrospective cohort study of consecutive female patients who received allografts in the RVOT position was conducted. All patients between 18 and 50 years of age were screened for cardiac, obstetric, and fetal outcomes of completed (≥20 weeks' gestation) pregnancies.

Results: In total, 196 women met the inclusion criteria, of whom 56 had 89 completed pregnancies. Information could be retrieved in 84 cases (94.4%). Mean maternal age was 29.6 ± 4.3 years, with 80 patients (95.2%) in New York Heart Association functional class I or II. The most common diagnosis was tetralogy of Fallot. All women survived pregnancy. There were 2 cases (2.4%) of heart failure (arrhythmic and diastolic dysfunction), 1 case (1.2%) of infection (chorioamnionitis), and 3 cases (3.6%) of pre-eclampsia. No other cardiac or obstetric events were reported. All children were born alive at a median gestational age of 38.4 weeks (interquartile range: 36.9 to 39.6 weeks), with a median birthweight of 2,930 g (interquartile range: 2,535 to 3,385 g). Seventeen (20.2%) were small for gestational age, and 20 (23.8%) were premature. Neonatal death was reported in 2 children (2.5%). Preconception pulmonary regurgitation was associated with an increased probability of pre-term labor (odds ratio: 2.610; 95% confidence interval: 1.318 to 5.172). Compared with the general Dutch population, pre-term delivery (25.0% vs. 7.4%, p < 0.001) and children small for gestational age (20.2% vs. 10.0%, p = 0.002) were more common.

Conclusions: Women in good cardiac health after RVOT reconstruction with allografts can safely experience pregnancy and labor. The higher incidence of pre-term delivery and children small for gestational age warrants special attention.
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http://dx.doi.org/10.1016/j.jacc.2018.03.522DOI Listing
June 2018

Internal Podalic Version and Breech Extraction: Enhancing Realistic Sensations in a Simulation Model.

Obstet Gynecol 2018 02;131(2):360-363

Departments of Obstetrics and Gynaecology, Pediatrics, and Epidemiology, Erasmus Medical Center, Rotterdam, and Managing Obstetrical Emergencies and Trauma (MOET), Stichting MOET, Tilburg, the Netherlands.

Background: Experience with internal podalic version and breech extraction is diminishing, especially in the younger generation of obstetricians. Simulation training is essential to teach and maintain these skills.

Instrument: We present a mannequin-based simulation method that enhances realistic sensations during training.

Experience: By positioning the fetal mannequin into a thin plastic bag filled with water, the impression of palpating, grabbing, and pulling the fetal feet through the plastic bag is similar to reaching feet through intact membranes. The unique approach of this realistic simulation model makes the experience fun and memorable, which contributes to the didactic value and success of the model.

Conclusion: The simulation model we present mimics the situation and sensation obstetricians experience while performing internal podalic version and breech extraction.
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http://dx.doi.org/10.1097/AOG.0000000000002424DOI Listing
February 2018

Prenatal influence of congenital heart defects on trajectories of cortical folding of the fetal brain using three-dimensional ultrasound.

Prenat Diagn 2017 Oct 4;37(10):1008-1016. Epub 2017 Sep 4.

Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Objective: The objective of the study is to investigate the prenatal influence of congenital heart defects (CHD) on trajectories of fetal cortical folding using three-dimensional ultrasound (3D US).

Method: We included 20 CHD fetuses and 193 controls for studying the fetal brain at 22, 26 and 32 weeks' gestational age (GA). The Sylvian, insula and parieto-occipital fissure (POF) depths were measured using 3D US, and reliability was evaluated. Doppler indices of the umbilical artery and middle cerebral artery were measured to calculate the cerebro-placental ratio. Associations between CHD and cortical folding were estimated using linear mixed models.

Results: Brain fissure measurements were successful in over 80% of 3D US scans, except for the POF at 32 weeks' GA (65%). All measurements showed a good reliability (intraclass correlation coefficients > 0.84). Growth trajectories of the left insula depth (ß = -2.753, 95% CI = -5.375; -0.130, p = 0.040) and right POF (ß = -3.762, 95% CI = -7.178; -0.346, p = 0.031) were decreased in CHD compared with controls, whereas growth rates were increased (ß = 0.014, 95% CI = 0.001; 0.027, p = 0.036 and ß = 0.024, 95% CI = 0.007; 0.041, p = 0.006). In contrast to controls, we found no associations between cerebro-placental ratio and cortical folding in CHD.

Conclusion: Fetal cortical folding can be evaluated reliably by measuring brain fissure depths. Trajectories of cortical folding between 22 and 32 weeks' GA seem to be influenced by CHD. © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.5135DOI Listing
October 2017

Comparison of the Actim Partus test and the fetal fibronectin test in the prediction of spontaneous preterm birth in symptomatic women undergoing cervical length measurement.

Eur J Obstet Gynecol Reprod Biol 2016 Nov 20;206:220-224. Epub 2016 Sep 20.

Obstetrics and Gynaecology, Academic Medical Centre, Amsterdam, Netherlands.

Objective: To compare the accuracy of the Actim Partus test and fetal fibronectin (fFN) test in the prediction of spontaneous preterm delivery within seven days in symptomatic women undergoing cervical length measurement.

Study Design: We performed a post-hoc analysis on frozen samples of a nationwide cohort study in all 10 perinatal centres in the Netherlands. We selected samples from women with signs of preterm labour between 24 and 34 weeks of gestational age and a cervical length below 30mm. Delivery within seven days after initial assessment was the primary endpoint. We calculated sensitivity, specificity, and positive and negative predictive values for the combination of both the Actim Partus test and fFN test with cervical length. A test was considered positive in case of a cervical length between 15 and 30mm with a positive Actim Partus or fFN test, and a cervical length below 15mm regardless the test result.

Results: In total, samples of 350 women were tested, of whom 69 (20%) delivered within seven days. Eighty-four women had a positive Actim Partus test and 162 women a positive fFN test, of whom 54 (64%) and 63 (39%) delivered within seven days, respectively. Ninety-seven women had a cervical length below 15mm, of whom 50 (52%) delivered within seven days. Sensitivity, specificity, positive and negative predictive values of combining cervical length with the Actim Partus test or the fFN test were 91%, 75%, 47% and 97%, and 96%, 58%, 36% and 98%, respectively.

Conclusion: According to this post-hoc study, in combination with cervical length, the Actim Partus test could be used as an alternative for the fFN test to identify women who will not deliver within seven days after presentation. Further evidence should be collected in a prospective comparative study.
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http://dx.doi.org/10.1016/j.ejogrb.2016.09.018DOI Listing
November 2016

Which Factors Contribute to False-Positive, False-Negative, and Invalid Results in Fetal Fibronectin Testing in Women with Symptoms of Preterm Labor?

Am J Perinatol 2017 Feb 21;34(3):234-239. Epub 2016 Jul 21.

Department of Obstetrics and Gynecology, Academic Medical Centre, Amsterdam, The Netherlands.

 We assessed the influence of external factors on false-positive, false-negative, and invalid fibronectin results in the prediction of spontaneous delivery within 7 days.  We studied symptomatic women between 24 and 34 weeks' gestational age. We performed uni- and multivariable logistic regression to estimate the effect of external factors (vaginal soap, digital examination, transvaginal sonography, sexual intercourse, vaginal bleeding) on the risk of false-positive, false-negative, and invalid results, using spontaneous delivery within 7 days as the outcome.  Out of 708 women, 237 (33%) had a false-positive result; none of the factors showed a significant association. Vaginal bleeding increased the proportion of positive fetal fibronectin (fFN) results, but was significantly associated with a lower risk of false-positive test results (odds ratio [OR], 0.22; 95% confidence intervals [CI], 0.12-0.39). Ten women (1%) had a false-negative result. None of the investigated factors was significantly associated with a significantly higher risk of false-negative results. Twenty-one tests (3%) were invalid; only vaginal bleeding showed a significant association (OR, 4.5; 95% CI, 1.7-12).  The effect of external factors on the performance of qualitative fFN testing is limited, with vaginal bleeding as the only factor that reduces its validity.
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http://dx.doi.org/10.1055/s-0036-1585466DOI Listing
February 2017

Interstitial 6q21q23 duplication - variant of variable phenotype and incomplete penetrance or benign duplication?

Mol Cytogenet 2016 2;9:43. Epub 2016 Jun 2.

Department of Clinical Genetics, Erasmus MC, Ee2475, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands.

Background: Chromosome 6q duplication syndrome is a chromosome abnormality associated with characteristic phenotypic features such as intellectual disability (ID), short stature, feeding difficulties, microcephaly, dysmorphic features (prominent forehead, downslanting palpebral fissures, flat nasal bridge, tented upper lip, micrognathia, short webbed neck) and joint contractures. Only a few cases of pure partial 6q trisomy have been published and the severity of the phenotype seems to depend on the breakpoint position. Unfortunately, most of these cases were identified using karyotyping or FISH, so breakpoints at the molecular level and thus gene content are not known.

Cases Presentation: We report the first two families with an interstitial 6q duplication identified by karyotyping where the gene content and breakpoints were characterized with microarray. In family 1, the 6q22.1q23.2 duplication was detected in a female patient with ID. In family 2, the 6q21q22.33 duplication was identified in a male fetus with multiple congenital malformations. In both families, the duplication seems to show phenotypic heterogeneity and in family 1 also incomplete penetrance suggesting the co-existence of an "additional hit" in affected patients. This "additional hit" was identified in the first family to be a microduplication in 16p11.2, a known susceptibility locus (SL) for neurodevelopmental disorders, that co-segregated with an abnormal phenotype in the affected family members.

Conclusions: Our study shows that interstitial 6q21q23 duplication may represent a private variant that is benign, but may also contribute to developmental disorders of variable expressivity in a "multi-hit" model. Finding the "additional hit" within the family is therefore very important for genetic counseling and assessment of the CNV penetrance within the particular family.
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http://dx.doi.org/10.1186/s13039-016-0253-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4891832PMC
June 2016

The impact of fetal gender and ethnicity on the risk of spontaneous preterm delivery in women with symptoms of preterm labor.

J Matern Fetal Neonatal Med 2016 Nov 24;29(21):3563-9. Epub 2016 Feb 24.

k Department of Obstetrics & Gynecology , Academic Medical Center , Amsterdam , Netherlands .

Objective: The objective of this study is to evaluate the relation among fetal gender, ethnicity, and preterm labor (PTL) and preterm delivery (PTD).

Methods: A secondary analysis was performed of a prospective cohort study including women with symptoms of PTL between 24 and 34 weeks. The proportion of women carrying a male or female fetus at the onset of PTL was calculated. Gestational age at delivery and risk of PTD of both fetal genders was compared and interaction of fetal gender and maternal ethnicity on the risk of PTD was evaluated.

Results: Of the 594 included women, 327 (55%) carried a male fetus. Median gestational age at delivery in women pregnant with a male fetus was 37 5/7 (IQR 34 4/7-39 1/7) weeks compared with 38 1/7 (IQR 36 0/7-39 5/7) weeks in women pregnant with a female fetus (p = 0.032). The risk of PTD did not differ significantly. In Caucasians, we did find an increased risk of PTD before 37 weeks in women pregnant with a male fetus (OR 1.9 (95% CI 1.2-3.0)).

Conclusions: The majority of women with PTL are pregnant with a male fetus and these women deliver slightly earlier. Race seems to affect this disparity.
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http://dx.doi.org/10.3109/14767058.2016.1139566DOI Listing
November 2016

Risk factors for preterm delivery: do they add to fetal fibronectin testing and cervical length measurement in the prediction of preterm delivery in symptomatic women?

Eur J Obstet Gynecol Reprod Biol 2015 Sep 10;192:79-85. Epub 2015 Jun 10.

Department of Obstetrics and Gynaecology, The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Australia.

Objective: To assess whether patient characteristics add to the fetal fibronectin test and cervical length measurement in the prediction of preterm delivery in symptomatic women.

Study Design: A nationwide prospective cohort study was conducted in all ten perinatal centres in the Netherlands. Women with symptoms of preterm labour between 24 and 34 weeks gestation with intact membranes were invited. In all women qualitative fibronectin testing (0.050 μg/mL cut-off) and cervical length measurement were performed. Only singleton pregnancies were included in this analysis. Logistic regression was used to construct two multivariable models to predict spontaneously delivery within 7 days: a model including cervical length and fetal fibronectin as predictors, and an extended model including all potential predictors. The models were internally validated using bootstrapping techniques. Predictive performances were assessed as the area under the receiver operator characteristic curve (AUC) and calibration plots. We compared the models' capability to identify women with a low risk to deliver within 7 days. 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: Seventy-three of 600 included women (12%) had delivered spontaneously within 7 days. The extended model included maternal age, parity, previous preterm delivery, vaginal bleeding, C-reactive protein, cervical length, dilatation and fibronectin status. Both models had high discriminative performances (AUC of 0.92 (95% CI 0.88-0.95) and 0.95 (95% CI 0.92-0.97) respectively). Compared to the model with fibronectin and cervical length, our extended model reclassified 38 women (6%) from low risk to high risk and 21 women (4%) from high risk to low risk. Preterm delivery within 7 days occurred once in both the reclassification groups.

Conclusion: In women with symptoms of preterm labour before 34 weeks gestation, a model that integrates maternal characteristics, clinical signs and laboratory tests, did not predict delivery within 7 days better than a model with only fibronectin and cervical length.
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http://dx.doi.org/10.1016/j.ejogrb.2015.05.004DOI Listing
September 2015

Prescribing patterns of antenatal corticosteroids in women with threatened preterm labor.

Eur J Obstet Gynecol Reprod Biol 2015 Sep 17;192:47-53. Epub 2015 Jun 17.

The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Australia.

Objective: To assess the impact of cervical length (CL) measurement and fetal fibronectin testing (fFN) on the clinicians' decision to prescribe antenatal corticosteroids (ACS) to women with symptoms of preterm labor.

Study Design: This is a secondary analysis of a prospective cohort study including women with symptoms of preterm labor and intact membranes between 24 and 34 weeks' gestation. We compared the proportion prescribed and completed ACS courses, preterm delivery within seven days and median intervals from ACS to delivery in four groups: group 1 CL<10 mm, group 2 CL 10-30 mm and positive fFN, group 3 CL 10-30 mm and negative fFN, group 4 CL>30 mm.

Results: ACS were prescribed to 63/65 (97%) women in group 1, 176/192 (91%) in group 2, 111/172 women (65%) in group 3 and 55/242 (23%) in group 4. In group 1, 42 (65%) women delivered within seven days, compared to 34 (18%) in group 2, 6 (3%) in group 3 and 3 (1%) in group 4. Median intervals between ACS and delivery were 6 days (IQR 3-61 days), 44 days (IQR 17-69 days), 53 days (IQR 37-77 days) and 66 days (IQR 43-78 days) in group 1, 2, 3 and 4 respectively.

Conclusion: ACS were prescribed frequently to women with a CL of 10-30 mm and a negative fFN test or a CL>30 mm. There is room for improvement in the prescription of ACS in these low risk women.
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http://dx.doi.org/10.1016/j.ejogrb.2015.06.008DOI Listing
September 2015

Risk stratification with cervical length and fetal fibronectin in women with threatened preterm labor before 34 weeks and not delivering within 7 days.

Acta Obstet Gynecol Scand 2015 Jul 29;94(7):715-721. Epub 2015 Apr 29.

Department of Obstetrics and Gynecology, Academic Medical Center, Amsterdam, the Netherlands.

Objective: To stratify the risk of spontaneous preterm delivery using cervical length (CL) and fetal fibronectin (fFN) in women with threatened preterm labor who remained pregnant after 7 days.

Design: Prospective observational study.

Setting: Nationwide cohort of women with threatened preterm labor from the Netherlands.

Population: Women with threatened preterm labor between 24 and 34 weeks with a valid CL and fFN measurement and remaining pregnant 7 days after admission.

Methods: Kaplan-Meier and Cox proportional hazards models were used to estimate cumulative percentages and hazard ratios (HR) for spontaneous delivery.

Main Outcome Measures: Spontaneous delivery between 7 and 14 days after initial presentation and spontaneous preterm delivery before 34 weeks.

Results: The risk of delivery between 7 and 14 days was significantly increased for women with a CL < 15 mm or a CL ≥15 to <30 mm and a positive fFN, compared with women with a CL ≥30 mm: HR 22.3 [95% confidence interval (CI) 2.6-191] and 14 (95% CI 1.8-118), respectively. For spontaneous preterm delivery before 34 weeks the risk was increased for women with a CL < 15 mm [HR 6.3 (95% CI 2.6-15)] or with a CL ≥15 to <30 mm with either positive fFN [HR 3.6 (95% CI 1.5-8.7)] or negative fFN [HR 3.0 (95% CI 1.2-7.1)] compared with women with a CL ≥ 30 mm.

Conclusions: In women remaining pregnant 7 days after threatened preterm labor, CL and fFN results can be used in risk stratification for spontaneous delivery.
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http://dx.doi.org/10.1111/aogs.12643DOI Listing
July 2015

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

Obstet Gynecol 2014 Jun;123(6):1185-1192

Departments of Obstetrics and Gynecology, Academic Medical Center and VU University Medical Center, Amsterdam, University Medical Center Utrecht, Utrecht, Maastricht University Medical Center, Maastricht, Máxima Medical Center, Veldhoven, Erasmus Medical Center, Rotterdam, Isala Clinics, Zwolle, University Medical Center Groningen, Groningen, Leiden University Medical Center, and Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands, Northwestern University Medical School, Chicago, Illinois, and The Robinson Institute, School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia; Clinical Epidemiology, Biostatistics and Bioinformatics and the Clinical Research Unit, Academic Medical Center, Amsterdam, and the Department of Clinical Chemistry and Haematology, University Medical Center Utrecht, Utrecht, The Netherlands.

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.
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http://dx.doi.org/10.1097/AOG.0000000000000229DOI Listing
June 2014

First-Trimester Detection of Surface Abnormalities: A Comparison of 2- and 3-Dimensional Ultrasound and 3-Dimensional Virtual Reality Ultrasound.

Reprod Sci 2014 Aug 18;21(8):993-999. Epub 2014 Jan 18.

Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

The aim was to determine the diagnostic performance of 3-dimensional virtual reality ultrasound (3D_VR_US) and conventional 2- and 3-dimensional ultrasound (2D/3D_US) for first-trimester detection of structural abnormalities. Forty-eight first trimester cases (gold standard available, 22 normal, 26 abnormal) were evaluated offline using both techniques by 5 experienced, blinded sonographers. In each case, we analyzed whether each organ category was correctly indicated as normal or abnormal and whether the specific diagnosis was correctly made. Sensitivity in terms of normal or abnormal was comparable for both techniques (P = .24). The general sensitivity for specific diagnoses was 62.6% using 3D_VR_US and 52.2% using 2D/3D_US (P = .075). The 3D_VR_US more often correctly diagnosed skeleton/limb malformations (36.7% vs 10%; P = .013). Mean evaluation time in 3D_VR_US was 4:24 minutes and in 2D/3D_US 2:53 minutes (P < .001). General diagnostic performance of 3D_VR_US and 2D/3D_US apparently is comparable. Malformations of skeleton and limbs are more often detected using 3D_VR_US. Evaluation time is longer in 3D_VR_US.
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http://dx.doi.org/10.1177/1933719113519172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126213PMC
August 2014

Pregnancy outcomes in women with aortic valve substitutes.

Am J Cardiol 2013 Feb 20;111(3):382-7. Epub 2012 Nov 20.

Department of Cardio-Thoracic Surgery, Erasmus University Medical Center, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1016/j.amjcard.2012.09.035DOI Listing
February 2013
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