Publications by authors named "Line Leduc"

47 Publications

Perinatal and cardiac outcomes of women with hypertrophic cardiomyopathy.

J Matern Fetal Neonatal Med 2021 Oct 15:1-6. Epub 2021 Oct 15.

Department of Obstetrics and Gynecology, Maternal Fetal Medicine Division, University Hospital Centre Sainte-Justine, Montreal, Canada.

Rationale: Pregnancy causes important physiologic stress for women with hypertrophic cardiomyopathy. Data regarding the impact of this condition on obstetrical outcomes is missing.

Objectives: Our objective was to report obstetrical and cardiac outcomes in pregnant women with hypertrophic cardiomyopathy and to assess the possible adverse effects of left ventricular outflow tract obstruction in pregnancy.

Study Design: This was a retrospective cohort study of pregnant women diagnosed with HCM and followed at single tertiary center between 1995 and 2019. Demographic, medical and surgical data, echocardiographic parameters, and pregnancy outcomes were abstracted through extensive chart review. Patients were divided into 2 groups: obstructive (maximal left ventricular outflow tract gradient over 30 mmHg) versus non-obstructive hypertrophic cardiomyopathy. Outcomes between groups were compared with -test, Mann-Whitney and Fisher's exact tests when appropriate.

Results: Eighteen women with 27 pregnancies were included. The study population was formed of 18 women with a total of 27 pregnancies that reached at least 20 weeks of gestation: 12 pregnancies in women with obstructive hypertrophic cardiomyopathy and 15 pregnancies in women with non-obstructive hypertrophic cardiomyopathy. Among the non-obstructive hypertrophic cardiomyopathy, 5 of them had been treated for their obstruction. One patient with obstructive hypertrophic cardiomyopathy had a medical termination of pregnancy for uncontrolled arrhythmia at 21 weeks. There were no maternal deaths. Left ventricular outflow tract obstruction was associated with increased cardiac events including arrhythmias and heart failure (5/12 versus 0/15;  = .006). Preterm birth occurred in more than 50% of cases, resulting from induced delivery for a maternal (40%) or fetal reason (60%). Most deliveries were late preterm between 34 and 36 6/7 weeks. In both groups, birthweight was mainly distributed below the 50th percentile (89%) and 35% of neonates were born small for gestational age defined as a birthweight below the 10th percentile. Most severe cases of small for gestational age (birthweight under the 5th percentile) were found in patients with treated obstructive hypertrophic cardiomyopathy.

Conclusion: Hypertrophic cardiomyopathy is associated with prematurity and small for gestational age. Left ventricular outflow tract obstruction is associated with adverse cardiac events including arrythmias or heart failure. Treated obstructive cardiomyopathy constitutes a sub-group of patients at high risk of severe small for gestational age and deserves a close surveillance. Therefore, fetal growth surveillance with ultrasound, early in the third trimester and doppler studies to assess the utero-placental perfusion in the second and third trimesters are warranted in all patients with hypertrophic cardiomyopathy regardless of the severity of their condition.
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http://dx.doi.org/10.1080/14767058.2021.1990883DOI Listing
October 2021

Pregnancies With Maternal Heart Disease: Small Babies, Big Problems?

Can J Cardiol 2021 May 14. Epub 2021 May 14.

Division of Pediatric Cardiology, Department of Pediatrics, Université de Sherbrooke and Centre de Recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.cjca.2021.04.025DOI Listing
May 2021

Maternal vitamin D, oxidative stress, and pre-eclampsia.

Int J Gynaecol Obstet 2021 Sep 21;154(3):444-450. Epub 2021 Jan 21.

Department of Obstetrics and Gynecology, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada.

Objective: To examine the associations between risk of pre-eclampsia and pregnancy levels of maternal 25-hydroxyvitamin D (25[OH]D) and oxidative stress biomarkers.

Methods: A nested case-control study (n = 99; 34 cases; 65 controls) within a prospective pregnancy cohort. Maternal 25(OH)D and oxidative stress markers (six isomers of F -isoprostanes; F -isoPs) were measured in plasma at 12-18 and 24-26 gestational weeks. Vitamin D deficiency was defined as 25[OH]D less than 50 nmol/L.

Results: Maternal vitamin D deficiency was associated with increased 8-iso-PGF (P = 0.037), 15(R)-PGF (P = 0.004), (±)5-iPF -VI (P = 0.026) at 12-18 weeks. Vitamin D deficiency was inversely associated with 8-iso-PGF (P = 0.019) and (±)5-iPF -VI isomer (P = 0.010) at 24-26 weeks. Both maternal vitamin D deficiency (adjusted odds ratio [aOR], 4.79; 95% confidence interval [CI], 1.67-13.75) and increased (±)5-iPF -VI (aOR, 2.46; 95% CI, 1.16-5.22) at 24-26 weeks were associated with risk of pre-eclampsia. However, the interaction test between 25(OH)D and (±)5-iPF -VI was not significant (P = 0.143).

Conclusion: Plasma 25(OH)D below 50 nmol/L was associated with increased oxidative stress levels during pregnancy as measured by two F -isoP isomers, including the well-studied marker 8-iso-PGF . Whether vitamin D-induced oxidative stress mediates the risk of pre-eclampsia warrants future study.
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http://dx.doi.org/10.1002/ijgo.13559DOI Listing
September 2021

No. 394-Stillbirth Investigation.

Authors:
Line Leduc

J Obstet Gynaecol Can 2020 Jan;42(1):92-99

Montréal, QC. Electronic address:

Objectives: To provide an investigation protocol to help health care providers determine the cause of a fetal death.

Options: Consideration has been given to protocols for the investigation of fetal death that are currently available in Canada and in other countries.

Outcomes: Identification of possible causes of stillbirth and their relationship to future pregnancies.

Evidence: Articles related to the etiology of fetal death were identified in a search of PubMed (June 2006 to September 2018), the Cochrane Library, and investigation protocols from the American College of Obstetricians and Gynecologists, the International Stillbirth Alliance Collaborative for Improving Classification of Perinatal Deaths, the Royal College of Obstetricians and Gynaecologists, the Queensland clinical guidelines, and the Reproductive Care Program of Nova Scotia.

Benefits: To provide better advice for women regarding possible causes of fetal death and implications for future pregnancies.

Validation: The evidence obtained was reviewed and evaluated by the Maternal-Fetal Medicine Committee and the Clinical Practice Obstetrics Committee of the Society of Obstetricians and Gynaecologists of Canada. The level of evidence and quality of the recommendation made was described using the Evaluation of Evidence criteria of the Canadian Task Force on Preventive Health Care.

Recommendations:
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http://dx.doi.org/10.1016/j.jogc.2019.04.001DOI Listing
January 2020

Directive clinique N 394 - Investigation sur la mortinaissance.

Authors:
Line Leduc

J Obstet Gynaecol Can 2020 01;42(1):100-108

Montréal (Qc).

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http://dx.doi.org/10.1016/j.jogc.2019.09.017DOI Listing
January 2020

Endogenous retrovirus-encoded Syncytin-2 contributes to exosome-mediated immunosuppression of T cells†.

Biol Reprod 2020 02;102(1):185-198

Université du Québec à Montréal, Department of Biological Sciences, Montreal, Quebec, Canada.

Modulation of the activation status of immune cell populations during pregnancy depends on placental villous cytotrophoblast (VCT) cells and the syncytiotrophoblast (STB). Failure in the establishment of this immunoregulatory function leads to pregnancy complications. Our laboratory has been studying Syncytin-2 (Syn-2), an endogenous retroviral protein expressed in placenta and on the surface of placental exosomes. This protein plays an important role not only in STB formation through its fusogenic properties, but also through its immunosuppressive domain (ISD). Considering that Syn-2 expression is importantly reduced in preeclamptic placentas, we were interested in addressing its possible immunoregulatory effects on T cells. Activated Jurkat T cells and peripheral blood mononuclear cells (PBMCs) were treated with monomeric or dimerized version of a control or a Syn-2 ISD peptide. Change in phosphorylation levels of ERK1/2 MAP kinases was selectively noted in Jurkat cells treated with the dimerized ISD peptide. Upon incubation with the dimerized Syn-2 ISD peptide, significant reduction in Th1 cytokine production was further demonstrated by ELISA and Human Th1/Th2 Panel Multi-Analyte Flow Assay. To determine if exosome-associated Syn-2 could also be immunosuppressive placental exosomes were incubated with activated Jurkat and PBMCs. Quantification of Th1 cytokines in the supernatants revealed severe reduction in T cell activation. Interestingly, exosomes from Syn-2-silenced VCT incubated with PBMCs were less suppressive when compared with exosome derived from VCT transfected with control small interfering RNA (siRNA). Our results suggest that Syn-2 is an important immune regulator both locally and systemically, via its association with placental exosomes.
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http://dx.doi.org/10.1093/biolre/ioz124DOI Listing
February 2020

Pregnancy in adults with repaired/unrepaired atrial septal defect.

J Thorac Dis 2018 Sep;10(Suppl 24):S2945-S2952

Adult Congenital Heart Centre, Montreal Heart Institute, CHUS Ste-Justine, Université de Montréal, Montreal, Canada.

Atrial septal defect (ASD) is the most common form of congenital heart disease. Left-to-right shunting leads to right ventricular (RV) volume overload with excessive pulmonary blood flow. Complications include exercise intolerance, pulmonary vascular disease, RV dysfunction, paradoxical thromboemboli, and atrial arrhythmias. Women with coexisting severe pulmonary hypertension should be counselled against pregnancy due to high incidence of maternal and fetal morbidity and mortality. In the absence of pulmonary hypertension, pregnancy is generally well tolerated in the setting of an ASD. Nevertheless, hemodynamic changes throughout gestation may increase the risk for complications, particularly in those with unrepaired ASDs. Arrhythmias are the most common cardiac event and occur in 4-5%, followed by paradoxical emboli in 2-5%. Obstetrical and neonatal complications include preeclampsia, a higher incidence of infants born small for gestational age, and higher fetal/perinatal mortality. Although there is no definitive evidence demonstrating superiority of an aggressive approach to ASD closure prior to pregnancy, it is currently common practice to electively close asymptomatic but large and/or hemodynamically significant ASDs prior to childbearing. Cardiology follow up during pregnancy should be adapted to clinical circumstances and includes transthoracic echocardiography during the second trimester and arrhythmia monitoring in the event of symptoms.
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http://dx.doi.org/10.21037/jtd.2017.10.130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174140PMC
September 2018

Obstetric and cardiac outcomes in women with Marfan syndrome and an aortic root diameter ≤ 45mm.

Eur J Obstet Gynecol Reprod Biol 2018 Nov 11;230:68-72. Epub 2018 Sep 11.

Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Sainte-Justine University Hospital, Qc,Canada; Université de Montréal, QC, Canada. Electronic address:

Objective: To assess obstetric and aortic outcomes in women with Marfan Syndrome according to aortic root diameter, in view of recommendations for caesarean delivery when the aortic root diameter is ≥40 mm in the 2010 American guidelines versus >45 mm in the 2011 European guidelines.

Study Design: In this retrospective cohort study conducted at Sainte-Justine Mother and Child Tertiary Hospital, 27 pregnancies in 20 women with Marfan Syndrome as defined by the international criteria, were followed prospectively between 1994 and 2017, after excluding women with prior aortic surgery. Obstetric and aortic outcomes were compared in 2 groups according to aortic root diameter: < 40 mm (21 pregnancies) and 40-45 mm (6 pregnancies).

Results: 21/27 women had a vaginal delivery. The caesarean section rate was 23.8% and 16.7% in women with diameter <40 mm and 40-45 mm respectively (p-value = 1), and perinatal outcome was similar across groups. Two women with a prepregnancy aortic root diameter <40 mm developed an acute type B dissection during the third trimester. Both had a family history of aortic dissection.

Conclusions: Vaginal delivery with rigorous pain control and avoidance of Valsalva maneuver may be safely considered in women with Marfan Syndrome and an aortic root diameter ≤45 mm. The risk of type B aortic dissection during pregnancy is hard to predict. Other factors such as family history of dissection and descending aorta size may play an important role, and this may modify our counselling.
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http://dx.doi.org/10.1016/j.ejogrb.2018.09.012DOI Listing
November 2018

Impact of maternal pulmonary insufficiency on fetal growth in pregnancy.

J Matern Fetal Neonatal Med 2020 Apr 19;33(7):1100-1106. Epub 2018 Sep 19.

Maternal-Fetal Medicine Division, Obstetrics & Gynecology Department, Sainte-Justine University Hospital, Montreal, Canada.

It is known that fetal growth is usually proportional to left-sided cardiac output (CO), which parallels the right-sided CO and that congenital right-sided lesions are usually associated with better perinatal outcomes than left-sided lesions. Our objective was to document whether newborns from mothers with severe residual pulmonary valve insufficiency (PI) after surgical tetralogy of Fallot (TOF) or pulmonary valve stenosis (PS) correction have lower birth weight (BW) than newborns from mothers with absent, mild, or moderate PI. This is a retrospective cohort study of women affected with repaired TOF and corrected PS with varied severity of residual PI. Exclusion criteria were: left ventricular dysfunction, left-sided valvular heart disease, other right-sided structural heart disease, chronic hypertension, substance addiction, and incomplete follow-up. Pregnancies were divided into three groups: absent or mild PI, moderate PI, and severe PI. A generalized linear model with normal dependent variable distribution was built and the parameter estimation made with Generalized Estimation Equations (GEE) to take into account repeated mother in data. Variables such as gestational age at birth, maternal age, smoking, and body mass index were tested with bivariate analyses to assess their effect on BW. Only gestational age remained in the adjusted model. A total of 45 patients were included (33 TOF and 12 PS) and 97 pregnancies were reported: 22 miscarriages (22.7%) (15 TOF, 7 PS) and 75 successful pregnancies (57 TOF, 18 PS). The patients were divided into three groups: 1) absent or mild PI, 2) moderate PI, and 3) severe PI groups, which comprised, respectively, 29 (15 TOF, 4 PS), 20 (10 TOF, 1 PS), and 26 successful pregnancies (8 TOF, 7 PS). Using three levels of PI (absent or mild, moderate, and severe), the unadjusted model showed a significant effect of level of PI on BW ( = .0118), as well as the adjusted model ( = .0263) with gestational age as a covariate. The estimated mean newborn's BW was 3055.8 g in the severe PI group, 3151.0 g in the moderate PI group, and 3376.4 g in the absent or mild group when adjusted for gestational age. Hence, we estimated that the mean newborn's BW is 321 g lower in the severe PI group compared with absent or mild PI group ((CI: 572.3; -68.9),  = .0087). Pregnancy is usually well tolerated in repaired TOF and corrected PS. Severe PI either from repaired TOF or PS is at higher risk of lower newborn's BW. Special attention must be paid to the severity of PI. Fetal growth surveillance in the third trimester is warranted.
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http://dx.doi.org/10.1080/14767058.2018.1514492DOI Listing
April 2020

Distinct inflammatory profile in preeclampsia and postpartum preeclampsia reveal unique mechanisms.

Biol Reprod 2019 01;100(1):187-194

Ste-Justine Hospital Research Center, Department of Obstetrics and Gynecology, Faculty of Medicine, Universite de Montreal, Quebec, Canada.

Preeclampsia (PE) is a poorly understood pregnancy complication. It has been suggested that changes in the maternal immune system may contribute to PE, but evidence of this remains scarce. Whilst PE is commonly experienced prepartum, it can also occur in the postpartum period (postpartum PE-PPPE), and the mechanisms involved are unknown. Our goal was to determine whether changes occur in the maternal immune system and placenta in pregnancies complicated with PE and PPPE, compared to normal term pregnancies. We prospectively recruited women and collected blood samples to determine the circulating immune profile, by flow cytometry, and assess the circulating levels of inflammatory mediators and angiogenic factors. Placentas were collected for histological analysis. Levels of alarmins in the maternal circulation showed increased uric acid in PE and elevated high-mobility group box 1 in PPPE. Analysis of maternal immune cells revealed distinct profiles in PE vs PPPE. PE had increased percentage of lymphocytes and monocytes whilst PPPE had elevated NK and NK-T cells as well. Elevated numbers of immune cells (CD45+) were detected in placentas from women that developed PPPE, and those were macrophages (CD163+). This work reveals changes within the maternal immune system in both PE and PPPE, and indicate a striking contrast in how this occurs. Importantly, elevated immune cells in the placenta of women with PPPE strongly suggest a prenatal initiation of the pathology. A better understanding of these changes will be beneficial to identify women at high risk of PPPE and to develop novel therapeutic targets.
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http://dx.doi.org/10.1093/biolre/ioy164DOI Listing
January 2019

Association Between Vitamin D Supplementation During Pregnancy and Offspring Growth, Morbidity, and Mortality: A Systematic Review and Meta-analysis.

JAMA Pediatr 2018 07;172(7):635-645

Centre Hospitalier Universitaire Saint-Justine Research Center, University of Montréal, Montréal, Quebec, Canada.

Importance: Whether vitamin D supplementation during pregnancy is beneficial and safe for offspring is unclear.

Objective: To systematically review studies of the effects of vitamin D supplementation during pregnancy on offspring growth, morbidity, and mortality.

Data Sources: Searches of Medline, Embase, and the Cochrane Database of Systematic Reviews were conducted up to October 31, 2017. Key search terms were vitamin D, pregnancy, randomized controlled trials, and offspring outcomes.

Study Selection: Randomized clinical trials of vitamin D supplementation during pregnancy and offspring outcomes.

Data Extraction And Synthesis: Two authors independently extracted data, and the quality of the studies was assessed. Summary risk ratio (RR), risk difference (RD) or mean difference (MD), and 95% CI were calculated using fixed-effects or random-effects meta-analysis.

Main Outcomes And Measures: Main outcomes were fetal or neonatal mortality, small for gestational age (SGA), congenital malformation, admission to a neonatal intensive care unit, birth weight, Apgar scores, neonatal 25-hydroxyvitamin D (25[OH]D) and calcium concentrations, gestational age, preterm birth, infant anthropometry, and respiratory morbidity during childhood.

Results: Twenty-four clinical trials involving 5405 participants met inclusion criteria. Vitamin D supplementation during pregnancy was associated with a lower risk of SGA (RR, 0.72; 95% CI, 0.52 to 0.99; RD, -5.60%; 95% CI, -0.86% to -10.34%) without risk of fetal or neonatal mortality (RR, 0.72; 95% CI, 0.47 to 1.11) or congenital abnormality (RR, 0.94; 95% CI, 0.61 to 1.43). Neonates with prenatal vitamin D supplementation had higher 25(OH)D levels (MD, 13.50 ng/mL; 95% CI, 10.12 to 16.87 ng/mL), calcium levels (MD, 0.19 mg/dL; 95% CI, 0.003 to 0.38 mg/dL), and weight at birth (MD, 75.38 g; 95% CI, 22.88 to 127.88 g), 3 months (MD, 0.21 kg; 95% CI, 0.13 to 0.28 kg), 6 months (MD, 0.46 kg; 95% CI, 0.33 to 0.58 kg), 9 months (MD, 0.50 kg; 95% CI, 0.01 to 0.99 kg), and 12 months (MD, 0.32 kg; 95% CI, 0.12 to 0.52 kg). Subgroup analysis by doses showed that low-dose vitamin D supplementation (≤2000 IU/d) was associated with a reduced risk of fetal or neonatal mortality (RR, 0.35; 95% CI, 0.15 to 0.80), but higher doses (>2000 IU/d) did not reduce this risk (RR, 0.95; 95% CI, 0.59 to 1.54).

Conclusions And Relevance: Vitamin D supplementation during pregnancy is associated with a reduced risk of SGA and improved infant growth without risk of fetal or neonatal mortality or congenital abnormality. Vitamin D supplementation with doses of 2000 IU/d or lower during pregnancy may reduce the risk of fetal or neonatal mortality.
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http://dx.doi.org/10.1001/jamapediatrics.2018.0302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137512PMC
July 2018

Pregnancy after heart transplantation: a well-thought-out decision? The Quebec provincial experience - a multi-centre cohort study.

Transpl Int 2018 Feb 26. Epub 2018 Feb 26.

Research Center, Montreal Heart Institute, University of Montreal, Montreal, QC, Canada.

Despite reports of successful pregnancies in heart transplant (HTx) recipients, many centers recommend their patients against maternity. We reviewed our provincial experience of pregnancy in HTx recipients by performing charts review of all known gestations following HTx in the province of Quebec (Canada), stratified between planned and unplanned pregnancies. Long-term survival was compared to HTx recipient women of childbearing age who did not become pregnant. Eighteen pregnancies, 56% unplanned, occurred in eight patients, 10.1 (2.6-27.0) years after HTx. Immunosuppression was CNI-based, with a mean dose increase of 48.3% (tacrolimus) and 26.5% (cyclosporine), without rejection. Cardiometabolic complications were high compared to the general Canadian population, including preeclampsia (15.4% vs. 5.5%), hypertension (38.5% vs. 4.6%), and diabetes (15.4% vs. 5.6%). Mean gestational age was 35.1 (23.4-39.6) weeks (72.2% live births; 53.8% prematurity). Mean birthweight was 2418 (660-3612) g. Serum creatinine increased during pregnancy, becoming significant after delivery (P = 0.0239), and returning to preconception level in all but three patients within a year. After 4.6 (1.2-17.2) years of follow-up, two rejection episodes occurred in one patient. Long-term mortality was similar to overall HTx women (Kaplan-Meier; P = 0.8071). Pregnancy in HTx carries high cardiometabolic complications and decreased kidney function, but is feasible with acceptable outcomes and no impact on mother's survival.
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http://dx.doi.org/10.1111/tri.13144DOI Listing
February 2018

Prenatal vitamin D status and offspring's growth, adiposity and metabolic health: a systematic review and meta-analysis.

Br J Nutr 2018 02 11;119(3):310-319. Epub 2018 Jan 11.

1Centre hospitalier universitaire Sainte-Justine Research Center,Montreal,QC H3T 1C5,Canada.

In this systematic review and meta-analysis of observational studies, we aimed to estimate the associations between prenatal vitamin D status and offspring growth, adiposity and metabolic health. We searched the literature in human studies on prenatal vitamin D status and offspring growth in PubMed, up to July 2017. Studies were selected according to their methodological quality and outcomes of interest (anthropometry, fat mass and diabetes in offspring). The inverse variance method was used to calculate the pooled mean difference (MD) with 95 % CI for continuous outcomes, and the Mantel-Haenszel method was used to calculate the pooled OR with 95 % CI for dichotomous outcomes. In all, thirty observational studies involving 35 032 mother-offspring pairs were included. Vitamin D status was evaluated by circulating 25-hydroxyvitamin D (25(OH)D) level. Low vitamin D status was based on each study's cut-off for low 25(OH)D levels. Low prenatal vitamin D levels were associated with lower birth weight (g) (MD -100·69; 95 % CI -162·25, -39·13), increased risk of small-for-gestational-age (OR 1·55; 95 % CI 1·16, 2·07) and an elevated weight (g) in infant at the age of 9 months (g) (MD 119·75; 95 % CI 32·97, 206·52). No associations were observed between prenatal vitamin D status and other growth parameters at birth, age 1 year, 4-6 years or 9 years, nor with diabetes type 1. Prenatal vitamin D may play a role in infant adiposity and accelerated postnatal growth. The effects of prenatal vitamin D on long-term metabolic health outcomes in children warrant future studies.
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http://dx.doi.org/10.1017/S0007114517003646DOI Listing
February 2018

Recurrent pre-eclampsia and subsequent cardiovascular risk.

Heart 2017 02 16;103(3):235-243. Epub 2016 Aug 16.

Institut national de santé publique du Québec, Montreal, Québec, Canada.

Objective: To determine the association between recurrent pre-eclampsia and long-term cardiovascular hospitalisation.

Methods: This study identified cardiovascular hospitalisations up to 25 years after pregnancy for all women who delivered between 1989 and 2013 in Québec, Canada. Exposures included recurrent and non-recurrent pre-eclampsia in women with two deliveries or more (N=606 820), and pre-eclampsia in women with only one delivery (N=501 761). Incidence, timing and risk of cardiovascular complications were calculated using accelerated failure time models adjusted for age, pre-existing disease, socioeconomic deprivation and period. Outcomes included a range of cardiovascular hospitalisations and procedures.

Results: Women with recurrent pre-eclampsia had higher incidence of cardiovascular hospitalisation (281.4 per 1000) than women with non-recurrent (167.7 per 1000) or no pre-eclampsia (72.6 per 1000). Mean time to cardiovascular hospitalisation was 10.5 years for recurrent, 11.6 years for non-recurrent and 12.7 years for no pre-eclampsia, a difference of 17.3% for recurrent and 8.7% for non-recurrent relative to no pre-eclampsia. Compared with no pre-eclampsia, recurrent pre-eclampsia was associated with 2 times the risk of heart disease (95% CI 1.69 to 2.29) and 3 times the risk of cerebrovascular disease (95% CI 2.25 to 4.05). Pre-eclampsia in women with one delivery was associated with 3 times greater risk of cardiovascular hospitalisation compared with no pre-eclampsia in women with two deliveries or more (95% CI 2.96 to 3.25).

Conclusions: Recurrent pre-eclampsia is associated with higher risk of future cardiovascular hospitalisation compared with no pre-eclampsia, and significantly shorter time to first cardiovascular event. Cardiovascular screening should be performed earlier for women with recurrent pre-eclampsia.
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http://dx.doi.org/10.1136/heartjnl-2016-309671DOI Listing
February 2017

Delivery at Term: Impact of University Education by Week of Gestation.

J Obstet Gynaecol Can 2016 Feb 26;38(2):118-24. Epub 2016 Feb 26.

University of Montreal Hospital Research Centre, Montreal QC; Sainte-Justine Hospital Research Centre, Montreal QC.

Objective: Data on risk factors for early term delivery are scant despite greater complications in infants born at 37 and 38 weeks' gestation. We determined the probability of delivery by gestational week at term according to level of maternal education, an established risk factor for preterm birth.

Methods: We analyzed 2 319 697 live singleton births at term (≥37 weeks) in Quebec from 1981 to 2010. We estimated hazard ratios with 95% confidence intervals (CI) of delivery according to level of maternal education, adjusting for individual characteristics. The main outcome measure was the probability of delivery at term by week of gestation for women with university education versus high school education.

Results: Early term birth at 37 and 38 weeks of gestation was less common for university-educated women (23.1%) than for high school-educated women (25.8%; P < 0.001). Compared with women with a high school education, university-educated women had a 15% lower probability of delivery at 37 to 38 weeks (95% CI: 0.84 to 0.86), a 4% lower probability of delivery at 39 weeks (95% CI: 0.96 to 0.97) and a 2% lower probability of delivery at 40 weeks (95% CI: 0.97 to 0.98). University-educated women were, however, more likely to deliver at 41 weeks.

Conclusion: A higher level of education was associated with longer duration of pregnancy at term. Women who were university-educated had a lower chance of delivery at 37, 38, 39, and even 40 weeks of gestation. Clinicians should be aware that women with lower levels of education are more likely to deliver earlier at term.
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http://dx.doi.org/10.1016/j.jogc.2015.11.001DOI Listing
February 2016

Oxidative conditions prevail in severe IUGR with vascular disease and Doppler anomalies.

J Matern Fetal Neonatal Med 2015 Aug;28(12):1471-5

Objective: Intrauterine growth restriction (IUGR) and prenatal exposure to oxidative stress are thought to lead to increased risks of cardiovascular disease later in life. The objective of the present study was to document whether cord blood oxidative stress biomarkers vary with the severity of IUGR and of vascular disease in the twin pregnancy model in which both fetuses share the same maternal environment.

Methods: This prospective cohort study involved dichorionic twin pairs, with one co-twin with IUGR. Oxidative stress biomarkers were measured in venous cord blood samples from each neonate of 32 twin pairs, and compared, according to severity of IUGR (IUGR <5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin.

Results: Oxidized Low-Density Lipoproteins (oxLDL) and Malondialdehyde (MDA) concentrations were increased proportionally in cases of severe IUGR. OxLDL concentrations were also increased in cases of IUGR with Doppler anomaly.

Conclusion: Our data indicate that severe IUGR, is related to a derangement in redox balance, illustrated by increased venous cord blood oxidative stress biomarkers concentrations. Severe IUGR and IUGR with abnormal Doppler can be translated into conditions with intense oxidative stress.
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http://dx.doi.org/10.3109/14767058.2014.957670DOI Listing
August 2015

Cardiac, obstetric, and fetal outcomes during pregnancy after biological or mechanical aortic valve replacement.

Can J Cardiol 2014 Jul 2;30(7):801-7. Epub 2014 Apr 2.

Department of Cardiac Surgery, Montreal Heart Institute, Université de Montréal, Montreal, Québec, Canada. Electronic address:

Background: The aim of this study was to assess pregnancy-related cardiac, maternal, and fetal outcomes in women who underwent aortic valve replacement (AVR).

Methods: From 1978-2011, 67 women < 40 years of age underwent 74 isolated AVRs (52 mechanical prostheses and 22 bioprostheses). All patients were prospectively followed at our dedicated valve clinic. Patients with Turner syndrome, previous hysterectomy, or tubal ligation were excluded. Cardiovascular, obstetric, and fetal outcomes were gathered from medical records and telephone interviews.

Results: A total of 27 pregnancies were reported in 14 patients (bioprosthetic AVR, n = 20; mechanical AVR, n = 7). In the bioprosthetic AVR group, the following adverse events occurred: hospitalizations for syncope (n = 2), prosthetic valve deterioration after pregnancy necessitating reintervention 6 months postpartum (n = 1), miscarriages (n = 9), and preterm birth (n = 1). In the mechanical AVR group, the following adverse events occurred: embolic myocardial infarctions with a decrease in systolic function (n = 2; 1 pregnancy was terminated and 1 was completed), miscarriage (n = 1), postpartum bleeding (n = 1), urgent cesarean section for placental abruption (n = 1), and preterm birth (n = 1).

Conclusions: Findings from this study suggest that pregnancies in women with mechanical AVRs are associated with a higher risk of cardiac and obstetric adverse events. Thus, from this limited cohort, it appears that pregnancies in women with bioprostheses are safer than those in patients with mechanical AVRs.
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http://dx.doi.org/10.1016/j.cjca.2014.03.036DOI Listing
July 2014

Predicting preterm birth in twin pregnancy: was the previous birth preterm? A Canadian experience.

J Obstet Gynaecol Can 2013 Sep;35(9):793-801

Department of Obstetrics and Gynaecology, Sainte Justine Hospital (CHU Sainte-Justine), Montreal QC; CHU Sainte-Justine Research Centre, Montreal QC; Maternal-Fetal Medicine Division, CHU Sainte-Justine, University of Montreal, Montreal QC.

Objective: Most studies determining risk of preterm birth in a twin pregnancy subsequent to a previous preterm birth are based on linkage studies or small sample size. We wished to identify recurrent risk factors in a cohort of mothers with a twin pregnancy, eliminating all known confounders.

Methods: We conducted a retrospective cohort study of twin births at a tertiary care centre in Montreal, Quebec, between 1994 and 2008, extracting information, including chorionicity, from patient charts. To avoid the effect of confounding factors, we included only women with a preceding singleton pregnancy and excluded twin-to-twin transfusion syndrome, fetal chromosomal/structural anomalies, fetal demise, and preterm iatrogenic delivery for reasons not encountered in both pregnancies. We used multiple regression and sensitivity analyses to determine recurrent risk factors.

Results: Of 1474 twin pregnancies, 576 met the inclusion criteria. Of these, 309 (53.6%) delivered before 37 weeks. Preterm birth in twins was strongly associated with preterm birth of the preceding singleton (adjusted OR 3.23; 95% CI 1.75 to 5.98). The only other risk factors were monochorionic twins (adjusted OR 1.82; 95% CI 1.21 to 2.73) and oldest or youngest maternal ages. Chronic or gestational hypertension, preeclampsia, and insulin-dependent diabetes during the singleton pregnancy did not significantly affect risk.

Conclusion: Preterm birth in a previous singleton pregnancy was confirmed as an independent risk factor for preterm birth in a subsequent twin pregnancy. This three-fold increase in risk remained stable regardless of year of birth, inclusion/exclusion of pregnancies following assisted reproduction, or defining preterm birth as < 34 or < 37 weeks' gestational age. Until the advent of optimal preventive strategies, close obstetric surveillance of twin pregnancies is warranted.
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http://dx.doi.org/10.1016/S1701-2163(15)30835-5DOI Listing
September 2013

Long QT syndrome in pregnancy: are vaginal delivery and use of oxytocin permitted? A case report.

J Obstet Gynaecol Can 2012 Nov;34(11):1073-1076

Department of Obstetrics and Gynecology, Sainte Justine Hospital, University of Montreal, Montreal QC.

Background: Patients with congenital long QT syndrome (LQTS) are at increased risk of ventricular arrhythmia, particularly during labour and the puerperium.

Case: A 28-year-old primigravida with known LQTS underwent induction of labour at 41 weeks' gestation using a Foley catheter balloon and IV oxytocin. Vaginal delivery with passive second stage and outlet forceps was undertaken with early epidural analgesia to prevent tachycardia and psychological stress. The patient gave birth to a healthy female, and had an uncomplicated postpartum period under continuous electrocardiogram monitoring.

Conclusion: Vaginal delivery with use of oxytocin for the induction of labour can be safely undertaken in patients with LQTS.
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http://dx.doi.org/10.1016/S1701-2163(16)35437-8DOI Listing
November 2012

Periodontal disease is not associated with preeclampsia in Canadian pregnant women.

J Periodontol 2012 Jul 22;83(7):871-7. Epub 2011 Dec 22.

Department of Obstetrics and Gynecology, University of Montreal, Montreal, Quebec, Canada.

Background: The findings from the studies on the relationship between periodontal disease and preeclampsia are inconsistent. The objective of this study is to examine the relationship between periodontal disease and preeclampsia.

Methods: A multicenter case-control study was conducted in Quebec, Canada. Preeclampsia was defined as blood pressure ≥140/90 mm Hg and ≥1+ proteinuria after 20 weeks of gestation. Periodontitis was defined as the presence of ≥4 sites with a probing depth ≥5 mm and a clinical attachment loss ≥3 mm at the same sites.

Results: A total of 92 preeclamptic women and 245 controls were analyzed. The percentage of periodontal disease was 18.5% in preeclamptic women and 19.2% in normotensive women (crude odds ratio [OR] = 0.96, 95% confidence interval [CI] = 0.52 to 1.77). After adjusting for confounding variables, periodontitis remained not associated with preeclampsia (adjusted OR = 1.13, 95% CI = 0.59 to 2.17).

Conclusion: This study does not support the hypothesis of an association between periodontal disease and preeclampsia.
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http://dx.doi.org/10.1902/jop.2011.110342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469482PMC
July 2012

Right ventricular endocarditis in a pregnant woman with a restrictive ventricular septal defect.

Congenit Heart Dis 2011 Nov-Dec;6(6):638-40. Epub 2011 May 5.

Adult Congenital Heart Disease Centre, Montreal Heart Institute Department of Obstetrics & Gynaecology, Sainte Justine Hospital, Université de Montréal, 5000 Belanger StreetEast, Montreal, QC, Canada.

A 22-year-old woman with a restrictive unoperated perimembranous ventricular septal defect was diagnosed with staphylococcal endocarditis during her 14th week of pregnancy. Echocardiography revealed a long, thin, and mobile vegetation along the right ventricular free wall that increased to 8 cm in length, with systolic protrusion across the pulmonary valve. The vegetation subsequently embolized, resulting in a pulmonary abscess. She responded favorably to intravenous antibiotic therapy maintained for a total of 6 weeks, with resolution of the intracardiac mass and pulmonary abscess. The remaining peripartum and postpartum course was relatively unremarkable. Percutaneous closure of the ventricular septal defect was successfully performed postpartum.
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http://dx.doi.org/10.1111/j.1747-0803.2011.00519.xDOI Listing
March 2012

Oxidized low-density lipoproteins in cord blood from neonates with intra-uterine growth restriction.

Eur J Obstet Gynecol Reprod Biol 2011 May 15;156(1):46-9. Epub 2011 Feb 15.

Department of Obstetrics and Gynaecology, Université de Montréal and Research Centre, CHU Sainte-Justine, Quebec, Canada.

Objective: We verified whether oxidative stress indices (oxidized low-density lipoproteins and malondialdehyde) and inflammatory biomarkers (circulating C-reactive protein, interleukin-6, tumour necrosis factor-α, serum amyloid A and soluble intercellular vascular cell adhesion molecule) are increased in the umbilical vein of placental insufficiency induced intra-uterine growth restricted neonates.

Study Design: The prospective cohort study, involving 3 tertiary care centers, consists of 200 consecutively recruited pregnant women carrying twins. We chose the twin pregnancy model because both fetuses share the same maternal environment, thereby avoiding potential confounding factors when comparing oxidative stress and inflammation biomarkers. We analysed only twin pairs with one with intra-uterine growth restriction (N=38) defined as fetal growth<10th percentile with abnormal Doppler of the umbilical artery. Blood samples were taken at birth from the umbilical vein. Intra-pair comparisons on the biomarkers were performed using the Student paired t-test.

Results: We observed increased cord blood levels of oxidized low-density lipoproteins, (2.394 ± .412 vs 1.296 ± .204, p=.003) but not of malondialdehyde in growth restricted neonates when compared to their normal counterparts. Although indices of inflammation tended to be increased in cord blood from growth restricted newborns, the difference did not reach statistical significance.

Conclusion: In the twin model, intra-uterine growth restriction is associated with low-density lipoprotein oxidation without apparent dysregulation of inflammation biomarkers.

Condensation: Increased oxidized low-density lipoproteins are observed in growth restricted twins compared to their co-twins with normal growth at birth.
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http://dx.doi.org/10.1016/j.ejogrb.2011.01.007DOI Listing
May 2011

Prediction of complications in pregnant women with cardiac diseases referred to a tertiary center.

Int J Cardiol 2011 Sep 24;151(2):209-13. Epub 2010 Jul 24.

Department of Obstetrics and Gynecology, Sainte Justine Hospital, University of Montreal, Montreal QC, Canada.

Background: Prediction of adverse maternal and neonatal events in women with heart disease is not well established. We aimed to assess cardiac, obstetrical and neonatal complications in pregnant women with heart disease referred to our tertiary care center and validate a previously proposed risk index.

Methods: We included 227 women with cardiac disease followed for 312 pregnancies at our tertiary center from 1992 to 2007. Cardiac risk was assessed using the previously proposed Cardiac Disease in Pregnancy (CARPREG) score and its association with maternal and neonatal outcomes was determined.

Results: Maternal cardiac lesions were predominantly congenital (81.4%). CARPREG risk was low (score=0) in 66.3% and intermediate (score=1) in 33.7% pregnancies. Maternal cardiac events complicated 7.4% pregnancies, with pulmonary edema occurring most frequently (3.8%). An intermediate score was associated with a higher rate of cardiac events (19.0% vs. 1.4%, odds ratio [OR] 15.6, 95% confidence interval (95%CI) 4.5-54.4, p<0.0001). Adverse events occurred in 27.5% neonates. Preterm deliveries occurred in 16.7% pregnancies, more commonly in patients with intermediate scores (OR 2.4, 95%CI 1.2-4.6, p=0.01). The sensitivity and negative predictive values of a low score were respectively 87% and 99% for total cardiac events and both 100% for primary cardiac events including pulmonary edema and sustained arrhythmia.

Conclusion: The CARPREG risk index has a high sensitivity and negative predictive value with regards to cardiac complications in pregnant women with heart disease. It may, therefore, be routinely used to improve the assessment of cardiac risk before and during pregnancy.
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http://dx.doi.org/10.1016/j.ijcard.2010.05.045DOI Listing
September 2011

An international trial of antioxidants in the prevention of preeclampsia (INTAPP).

Am J Obstet Gynecol 2010 Mar;202(3):239.e1-239.e10

Department of Obstetrics and Gynecology, Hôpital Ste-Justine, Université de Montréal, Montreal, QC, Canada.

Objective: We sought to investigate whether prenatal vitamin C and E supplementation reduces the incidence of gestational hypertension (GH) and its adverse conditions among high- and low-risk women.

Study Design: In a multicenter randomized controlled trial, women were stratified by the risk status and assigned to daily treatment (1 g vitamin C and 400 IU vitamin E) or placebo. The primary outcome was GH and its adverse conditions.

Results: Of the 2647 women randomized, 2363 were included in the analysis. There was no difference in the risk of GH and its adverse conditions between groups (relative risk, 0.99; 95% confidence interval, 0.78-1.26). However, vitamins C and E increased the risk of fetal loss or perinatal death (nonprespecified) as well as preterm prelabor rupture of membranes.

Conclusion: Vitamin C and E supplementation did not reduce the rate of preeclampsia or GH, but increased the risk of fetal loss or perinatal death and preterm prelabor rupture of membranes.
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http://dx.doi.org/10.1016/j.ajog.2010.01.050DOI Listing
March 2010

Fetal programming of atherosclerosis: possible role of the mitochondria.

Eur J Obstet Gynecol Reprod Biol 2010 Apr 6;149(2):127-30. Epub 2010 Jan 6.

Department of Obstetrics and Gynaecology, Université de Montréal, Research Centre, CHU Sainte-Justine, Montreal, Quebec, Canada.

Growing evidence indicates that being small size at birth from malnutrition is associated with an increased risk of developing type 2 diabetes (T2D), metabolic syndrome and cardiovascular disease in adulthood. Atherosclerosis is common to these aforementioned disorders, and oxidative stress and chronic inflammation are now considered as initiating events in its development, with endothelial cell dysfunction being an early, fundamental step. According to the fetal programming hypothesis, growth-restricted neonates exposed to placental insufficiency exhibit endothelial cell dysfunction very early in life that later on predisposes them to atherosclerosis. Although many investigations have reported early alterations in vascular function in children and adolescents with low birth weight, the mechanisms of such fetal programming of atherosclerosis remain largely unknown. Experimental studies have demonstrated that low birth weight infants are prenatally subjected to conditions of oxidative stress and inflammation that might be involved in the later occurrence of atherosclerosis. Arterial endothelial dysfunction has been encountered in term infants, children and young adults with low birth weight. The loss of appropriate endothelium function with decreased nitric oxide production or activity, manifested as impaired vasodilatation, is considered a basic step in atherosclerosis development and progression. Several lines of evidence indicate that mitochondrial damage is central to this process and that reactive oxygen species (ROS) may act as a double-edged sword. On the one hand, it is well-accepted that the mitochondria are a major source of chronic ROS production under physiological conditions. On the other hand, it is known that ROS generation damages lipids, proteins and mitochondrial DNA, leading to dysregulated mitochondrial function. Elevated mitochondrial ROS production is associated with endothelial cell dysfunction as well as vascular smooth muscle cell proliferation and apoptosis. Smoking, obesity, insulin-resistant T2D, hypercholesterolemia, hyperglycaemia and hypertriglyceridaemia, major, traditional precursors of atherosclerosis, are all linked to mitochondrial dysfunction. This review focuses on proof of in utero programming resulting from chronic exposure to oxidative stress and inflammation as a cause of atherosclerosis. Endothelial cell dysfunction may be the initial injury arising from adverse antenatal conditions and responsible for the early changes in vascular function seen in children. After considering the critical role of the mitochondria in atherogenesis through endothelial function abnormalities, we propose that placental mitochondrial dysfunction is present in cases of placental insufficiency and may be critical in fetal programming of atherosclerosis.
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http://dx.doi.org/10.1016/j.ejogrb.2009.12.005DOI Listing
April 2010

Fetal transfusion of red blood cells for alloimmunization: validity of a published equation.

Fetal Diagn Ther 2009 30;25(4):379-84. Epub 2009 Sep 30.

Department of Obstetrics and Gynecology, Sainte-Justine Hospital, Montreal, Que., Canada.

Objective: To validate the equation published in 1990 by Leduc et al. for red blood cell fetal transfusion where fetoplacental blood volume (VO) = 100 ml/kg, then improve its precision.

Methods: We reviewed 101 fetal transfusions among 32 patients. We analyzed risk factors for an inaccurate estimation with uni- and multivariate analysis. We compared the obtained Leduc formula with three other published equations.

Results: Fetal weight and gestational age were risk factors for an inaccurate estimation of the final Hct. Before 32 weeks the estimation of VO was 120 ml/kg instead of 100 ml/kg. All formulae overestimated the mean expected Hct value. However, expected Hct estimated by Leduc's formula is the nearest of the observed final Hct.

Conclusion: Leduc's equation seems to be accurate, but less so for the youngest fetuses. We propose an adapted formula VO according to gestational age and fetal weight estimation.
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http://dx.doi.org/10.1159/000236150DOI Listing
December 2009

Imaging in the management of abdominal pregnancy: a case report and review of the literature.

J Obstet Gynaecol Can 2009 Jan;31(1):57-62

Department of Obstetrics and Gynecology, CHU Sainte-Justine, Montreal QC.

Background: Abdominal pregnancy is a rare condition that is potentially life-threatening for the mother.

Case: A 29-year-old woman presented with abdominal pain at 17 weeks of pregnancy. An ultrasound scan demonstrated an active abdominal pregnancy. MRI was used for placental localization. After discussion with the woman, it was decided to proceed to termination of the pregnancy. A pelvic angiogram was performed to localize placental vascularization. Both uterine arteries were embolized. Catheterization of the ovarian arteries identified that the right ovarian artery was one of the main vessels supplying the placenta. Selective embolization was performed. Laparotomy was then performed with removal of the fetus, but the placenta was left in place. Use of methotrexate was not required in the postoperative period. The patient was discharged on the seventh postoperative day. Serum BhCG became negative within one month.

Conclusion: In the management of abdominal pregnancy, the use of imaging and radio-interventional techniques is critical in minimizing surgical and post-surgical interventions.
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http://dx.doi.org/10.1016/s1701-2163(16)34055-5DOI Listing
January 2009

Incidence and risk factors of amniotic fluid embolisms: a population-based study on 3 million births in the United States.

Am J Obstet Gynecol 2008 Jul 4;199(1):49.e1-8. Epub 2008 Mar 4.

Department of Obstetrics and Gynecology, CHU Sainte-Justine, University of Montreal, Montreal, QC, Canada.

Objective: Amniotic fluid embolism (AFE) is a condition occurring during delivery that can lead to severe maternal morbidity and mortality. Given the rarity of its occurrence, current estimates and predictors of the incidence and outcomes are often difficult to obtain.

Study Design: We conducted a population-based cohort study on 3 million birth records in the Healthcare Cost and Utilization Project-Nationwide Inpatient Sample from 1999 to 2003 to estimate the incidence and case fatality of AFEs. Logistic regression was used to calculate the odds ratio (OR) and corresponding 95% confidence intervals (CIs) of demographic and obstetrical determinants of AFEs and fatal AFEs.

Results: The overall incidence of AFE was 7.7 per 100,000 births (95% CI 6.7 to 8.7), with a case fatality rate of 21.6% (95% CI 15.5 to 27.6%). AFE was associated with maternal age greater than 35 (OR 2.2, 95% CI 1.5 to 2.1), placenta previa (OR 30.4, 95% CI 15.4 to 60.1), and cesarean delivery (OR 5.7, 95% CI 3.7 to 8.7). Although AFEs were not significantly associated with induction of labor (OR 1.5, 95% CI 0.9 to 2.3), they were associated with preeclampsia, abruptio placentae, and the use of forceps. Among women with an AFE, common demographic or obstetrical determinants were not predictive of maternal mortality.

Conclusion: AFE is a rare but serious condition that is associated with advanced maternal age, placental pathologies, and cesarean deliveries. Further research on the treatment of this condition is necessary.
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http://dx.doi.org/10.1016/j.ajog.2007.11.061DOI Listing
July 2008

Dalteparin and low-dose aspirin in the prevention of adverse obstetric outcomes in women with inherited thrombophilia.

J Obstet Gynaecol Can 2007 Oct;29(10):787-93

Department of Obstetrics and Gynecology, Sainte-Justine Hospital, University of Montreal, Montreal QC.

Objective: To evaluate the benefit of treatment with dalteparin and low-dose aspirin (ASA) in the prevention of obstetric complications in women with inherited thrombophilia.

Methods: A retrospective chart review identified women who had had at least one pregnancy complicated by severe early-onset preeclampsia, placental abruption, fetal growth restriction (FGR), or fetal death. The following inherited thrombophilias were included: deficiencies of antithrombin, protein C, or protein S, and mutations of factor V Leiden (G1691A), factor II (G20210A), or methylenetetrahydrofolate reductase C677T.

Results: The records of 43 women with 110 pregnancies were included in the study. Anticoagulant prophylaxis was administered using dalteparin in 13 pregnancies, ASA with dalteparin in 26, and ASA alone in 11. Dalteparin alone and ASA alone showed equivalent effects in preventing preeclampsia and FGR. Combined dalteparin and ASA significantly decreased the risk of preeclampsia (odds ratio [OR] 0.80; 95% confidence intervals [CI] 0.70-0.91, P = 0.001) and FGR (OR 0.70; 95% CI 0.60-0.82, P = 0.001).

Conclusion: Data from this retrospective cohort study suggest that combined treatment with dalteparin and ASA decreases the risk of preeclampsia by 20% and the risk of FGR by 30% in women with inherited thrombophilia.
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http://dx.doi.org/10.1016/s1701-2163(16)32641-xDOI Listing
October 2007
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