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

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.

No. 394-Stillbirth Investigation.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

Objectif : La plupart des études qui cherchent à déterminer le risque d'accouchement préterme dans le cadre d'une grossesse gémellaire se déroulant à la suite d'un accouchement préterme sont fondées sur des études de liaison ou des échantillons de faible envergure. Nous souhaitions identifier les facteurs de risque récurrents au sein d'une cohorte de mères connaissant une grossesse gémellaire, en éliminant toutes les variables de confusion connues. Méthodes : Nous avons mené une étude de cohorte rétrospective qui portait sur les grossesses gémellaires ayant donné lieu à un accouchement au sein d'un centre de soins tertiaires de Montréal, au Québec, entre 1994 et 2008; nous avons extrait les données requises (dont la chorionicité) des dossiers des patientes. Pour éviter l'effet des facteurs de confusion, nous n'avons inclus que des femmes ayant déjà connu une grossesse monofœtale et avons exclu les cas de syndrome transfuseur-transfusé, d'anomalies chromosomiques / structurelles fœtales, de décès fœtal et d'accouchement préterme iatrogène pour des motifs n'ayant pas été constatés au cours des deux grossesses. Nous avons fait appel à des analyses de régression multiple et de sensibilité pour déterminer les facteurs de risque récurrents. Résultats : Parmi les 1 474 grossesses gémellaires recensées, 576 ont satisfait aux critères d'inclusion. Parmi celles-ci, 309 (53,6 %) accouchements ont eu lieu avant 37 semaines. L'accouchement préterme dans le cadre d'une grossesse gémellaire à été fortement associé au fait d'avoir connu un accouchement préterme dans le cadre de la grossesse monofœtale précédente (RC corrigé, 3,23; IC à 95 %, 1,75 - 5,98). Les seuls autres facteurs de risque ont été les jumeaux monozygotes (RC corrigé, 1,82; IC à 95 %, 1,21 - 2,73) et les âges maternels les plus vieux ou les plus jeunes. La présence d'une hypertension chronique ou gestationnelle, d'une prééclampsie et d'un diabète insulino-dépendant au cours de la grossesse monofœtale n'a pas exercé un effet significatif sur le risque. Conclusion : Le fait d'avoir connu un accouchement préterme dans le cadre d'une grossesse monofœtale précédente a été confirmé comme étant un facteur de risque indépendant d'accouchement préterme dans le cadre d'une grossesse gémellaire subséquente. Ce triplement du risque est demeuré stable, peu importe l'année de naissance, l'inclusion / exclusion des grossesses attribuables à la procréation assistée ou la définition de l'accouchement préterme comme étant < 34 ou < 37 semaines de gestation. Jusqu'à ce que des stratégies de prévention optimales soient mises au point, la mise en œuvre d'une étroite surveillance obstétricale s'avère justifiée dans les cas de grossesse gémellaire.

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

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.

Perinatal and cardiac outcomes of women with hypertrophic cardiomyopathy.

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 t-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; p = .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.

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

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 F2 -isoprostanes; F2 -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-PGF2α (P = 0.037), 15(R)-PGF2α (P = 0.004), (±)5-iPF2α -VI (P = 0.026) at 12-18 weeks. Vitamin D deficiency was inversely associated with 8-iso-PGF2α (P = 0.019) and (±)5-iPF2α -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-iPF2α -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-iPF2α -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 F2 -isoP isomers, including the well-studied marker 8-iso-PGF2α . Whether vitamin D-induced oxidative stress mediates the risk of pre-eclampsia warrants future study.

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

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.

Impact of maternal pulmonary insufficiency on fetal growth in pregnancy.

Rationale: 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.Objective: 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.Methods: 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.Results: 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 (p = .0118), as well as the adjusted model (p = .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), p = .0087).Conclusions: 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.

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

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.

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

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.

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

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.

Pregnancy in adults with repaired/unrepaired atrial septal defect.

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.

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

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.

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

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.