BackgroundThere is a paucity of data regarding sex-related differences on cardiac outcomes in the context of transposition of the great arteries (TGA) with a systemic right ventricle and biventricular physiology (sRV-biV). Moreover, the long-term impact of pregnancy on cardiac outcomes remains unknown.ObjectivesThe purpose of this study was to identify sex-related differences and the influence of pregnancy on cardiac outcomes in TGA sRV-biV population.MethodsA retrospective cohort study was conducted on 213 adults with TGA sRV-biV, 82 (38.4%) women, age 42.6 ± 12.8 years, with a median follow-up of 16 years. Cardiac events, interventions, last follow-up sRV-biV dysfunction, and heart failure (HF) medications were compared between men vs women, and women with vs without pregnancies resulting in live births.ResultsWomen had a lower incidence of nonsustained ventricular tachycardia (HR: 1.80; 95% CI: 1.04-3.09, P = 0.035) and nonsignificantly fewer HF-related hospitalizations than men (HR: 2.10; 95% CI: 0.95-4.67, P = 0.069) in univariable analysis. At the last follow-up, women had a lower prevalence of moderate to severe sRV-biV dysfunction than men (P < 0.001) and were less frequently prescribed HF therapy. Women had fewer implantable cardioverter-defibrillators for primary prevention than men (P = 0.016), with no difference for secondary prevention. Women who had pregnancies resulting in live births (N = 47), had a high prevalence of cardiac events in the 15 (IQR: 9-28) years following pregnancy with no significant differences with those without (N = 32) pregnancies.ConclusionsWomen with a sRV-biV have fewer adverse cardiovascular events than men. Due to sRV-biV, pregnancy remains with high maternal risk but is not associated with worse long-term cardiac outcomes under rigorous multidisciplinary cardio-obstetrical care.

Introduction: Transposition of the great arteries (TGA) with a systemic right ventricle (sRV) and biventricular physiology is associated with increased morbidity and mortality. There is a paucity of data regarding sex-related differences in outcomes in the context of a sRV. Moreover, pregnancy has been associated with deterioration of sRV function in short-term post-partum follow-up, but the long-term impact remains largely unknown. Methods and Results: A retrospective cohort study was conducted on 214 adults, age 44.7±12.3 years, with a sRV and biventricular physiology followed for a median of 13 years at an adult congenital heart disease center. No sex-related difference was identified in the prevalence of atrial or ventricular arrhythmias, permanent pacemaker implantation, hospitalization for heart failure, systemic atrio-ventricular valve intervention, heart transplant, or cardiac death. Among the 82 (38.3%) women, age 44.0±12.5 years, 43 (52.4%) had at least one full-term pregnancy. Women had a lower prevalence of moderate to severe sRV dysfunction than men (21% vs 42.6%, p=0.001) despite similar ages. Beta-blockers (p=0.008), furosemide (p=0.012), and mineralocorticoid receptor antagonists (p=0.028) were less frequently prescribed to women than men. Women had fewer implantable cardioverter-defibrillators (ICDs) for primary prevention than men (3.7% vs 13.6%, p=0.016), with no difference in the prevalence of secondary prevention ICDs (1.2% vs 2.3%, p=1). The four women with a prohibitive maternal mortality risk (modified WHO class IV) complied with recommendations to avoid pregnancy. After excluding these 4 women, no differences regarding frequency of adverse cardiac events, age at the time of event, and proportion with moderate or severe sRV dysfunction were observed in women with (N=43) and without (N=35) pregnancies during 14 years of follow-up. Conclusions: Women with TGA and a sRV had a lower prevalence of moderate to severe systemic ventricular dysfunction than men, along with a lower proportion of primary prevention ICDs. Following risk assessment and counselling with contraindication of pregnancy in the highest risk subgroup, pregnancy had no impact on long-term cardiac outcomes.

( Int J Gynecol Obstet . 2021;154:444–450) Preeclampsia (PE) is a serious and complex pregnancy-related disorder with negative effects on both the mother and fetus. Prevention is vital to reduce 18% of maternal mortality that results from PE in the United States each year. After years of study, its causes and mechanisms have not yet been fully unraveled. A recent review and analysis have shown an association between maternal vitamin D levels during pregnancy and an increased risk of PE.

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.

The care of children with heart diseases has tremendously improved in the past few decades. Most children with heart conditions, even those with the most complex conditions, now grow up and reach adulthood, find jobs, fall in love, and hope to have children of their own. Pregnancy comes with its share of joy along with, inevitably, an increased but necessary hemodynamic burden to sustain the life of two beings instead of one. Despite our best efforts, women with acquired and congenital heart diseases often have residual structural heart lesions or ongoing functional cardiac impairments that will chronically increase the cardiovascular load, which may very well worsen during pregnancy. The consequences are felt by both the pregnant woman and her baby. These women are more at risk of cardiac failure, arrhythmia, hypertension, stroke, bleeding, miscarriage, and maternal mortality, especially those with a severe congenital heart disease. 1 Hardee I Wright L McCracken C Lawson E Oster ME Maternal and neonatal outcomes of pregnancies in women with congenital heart disease: a meta-analysis. J Am Heart Assoc. 2021; 10e017834 Crossref PubMed Scopus (17) Google Scholar , 2 Roos-Hesselink JW Ruys TP Stein JI et al. Outcome of pregnancy in patients with structural or ischaemic heart disease: results of a registry of the European Society of Cardiology. Eur Heart J. 2013; 34: 657-665 Crossref PubMed Scopus (321) Google Scholar , 3 Silversides CK Grewal J Mason J et al. Pregnancy outcomes in women with heart disease: the CARPREG II study. J Am Coll Cardiol. 2018; 71: 2419-2430 Crossref PubMed Scopus (297) Google Scholar As for the fetus, there is increased risk of intrauterine growth restriction, intrauterine fetal demise, prematurity, being small for gestational age (SGA), and neonatal mortality. 1 Hardee I Wright L McCracken C Lawson E Oster ME Maternal and neonatal outcomes of pregnancies in women with congenital heart disease: a meta-analysis. J Am Heart Assoc. 2021; 10e017834 Crossref PubMed Scopus (17) Google Scholar ,4 Drenthen W Pieper PG Roos-Hesselink JW et al. Outcome of pregnancy in women with congenital heart disease: a literature review. J Am Coll Cardiol. 2007; 49: 2303-2311 Crossref PubMed Scopus (482) Google Scholar Cardiac Risk Score to Predict Small for Gestational Age Infants in Pregnant Women With Heart DiseaseCanadian Journal of CardiologyVol. 37Issue 12PreviewOne of the most common fetal complications in pregnant women with cardiovascular disease is a small for gestational age (SGA) neonate, which is associated with a higher risk of perinatal morbidity/mortality and poor long-term health outcomes. The objective of this study was to identify cardiac determinants and derive a risk score for clinically relevant SGA < 5th percentile (SGA-5th). Full-Text PDF

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

Abstract 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 1A protocol should be used to investigate the possible cause of a fetal death (II-2A). 2The diagnostic workup after stillbirth should depend on the specific clinical features per case (II-2A). 3Parents should be advised that no specific cause is found in almost half of stillbirths (II-2B). 4Placental and cord examination, autopsy, and cytogenetic evaluation should be recommended to all parents, regardless of cultural background, to try to explain the cause of fetal death (II-2B). 5Autopsy examination may only be performed with the informed consent of the parents (III-A). 6In cases where parents do not consent for autopsy, minimally invasive postmortem examination should be offered using magnetic resonance imaging, where available, combined with less invasive histological tissue sampling (III-B).

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:

To report obstetrical and cardiovascular outcomes in pregnant women with hypertrophic cardiomyopathy (HCM). This a retrospective cohort study of pregnant women diagnosed with HCM followed in a single tertiary center. Demographic, medical and surgical data, echocardiographic parameters, medication and pregnancy outcomes were abstracted through extensive chart review. Patients were divided in 2 groups: obstructive (gradient ≥ 30 mmHg) versus non-obstructive HCM. Outcomes between groups were compared with t-test, Mann-Whitney and Fisher's exact tests when appropriate. Results are summarized in the table. Data comprised 19 women with 29 pregnancies. One patient with obstructive HCM had a medical termination of pregnancy for uncontrolled arrythmia at 21 weeks. No maternal death occurred. No patient complicated of preeclampsia or thromboembolic events. Left ventricular outflow (LVOT) obstruction was associated with increased adverse cardiac events including arrythmias and heart failure (6/14 versus 0/15; p=0.006). Twenty pregnancies were on β-blockers (69%). HCM is associated with significant prematurity and IUGR. LVOT obstruction is associated with adverse cardiac events. These remain important for pregnancy counselling.

Objectifs Fournir un protocole d'investigation pour aider les fournisseurs de soins de santé à déterminer la cause d'une mort fœtale. Options Une attention particulière a été portée aux protocoles d'investigation sur la mort fœtale disponibles au Canada et dans d'autres pays à l'heure actuelle. Résultats Déterminer les causes possibles d'une mortinaissance et leur incidence sur les grossesses subséquentes. Données probantes Afin de retenir des articles relatifs à l’étiologie de la mort fœtale, des recherches ont été effectuées dans les bases de données PubMed (juin 2006 à septembre 2018) et Cochrane Library, et dans les protocoles d'investigation de l'American College of Obstetricians and Gynecologists, de l'International Stillbirth Alliance Collaborative for Improving Classification of Perinatal Deaths, du Royal College of Obstetricians and Gynaecologists, des Queensland Clinical Guidelines et du Reproductive Care Program of Nova Scotia. Avantages Offrir les meilleurs conseils aux femmes quant aux causes possibles d'une mort fœtale et de leurs incidences sur des grossesses subséquentes. Méthodes de validation Le comité de médecine fœto-maternelle et le comité de pratique clinique – obstétrique de la Société des obstétriciens et gynécologues du Canada ont analysé et évalué les données probantes obtenues. La qualité des données et des recommandations a été déterminée à l'aide des critères d’évaluation des données du Groupe d'étude canadien sur les soins de santé préventifs. RECOMMANDATIONS 1Il y a lieu d'utiliser un protocole pour enquêter sur la cause possible d'une mort fœtale (II-2A). 2Il convient de réaliser un bilan diagnostic après une mortinaissance en fonction des caractéristiques cliniques précises de chaque cas (II-2A). 3Il faut informer les parents du fait qu'aucune cause précise n'est déterminée dans près de la moitié des cas de mortinaissance (II-2B). 4Il y a lieu de recommander l'examen du cordon ombilical et du placenta, l'autopsie et l’évaluation cytogénétique à tous les parents, sans égard à leur héritage culturel, pour tenter d'expliquer la cause de la mort fœtale (II-2B). 5L'autopsie ne peut pas être réalisée sans le consentement éclairé des parents (III-A). 6Dans les cas où les parents ne consentent pas à l'autopsie, il y a lieu d'offrir un examen post mortem minimalement invasif au moyen de l'imagerie par résonance magnétique, lorsque disponible, combinée à un prélèvement histologique moins effractif que l'autopsie (III-B). Fournir un protocole d'investigation pour aider les fournisseurs de soins de santé à déterminer la cause d'une mort fœtale. Une attention particulière a été portée aux protocoles d'investigation sur la mort fœtale disponibles au Canada et dans d'autres pays à l'heure actuelle. Déterminer les causes possibles d'une mortinaissance et leur incidence sur les grossesses subséquentes. Afin de retenir des articles relatifs à l’étiologie de la mort fœtale, des recherches ont été effectuées dans les bases de données PubMed (juin 2006 à septembre 2018) et Cochrane Library, et dans les protocoles d'investigation de l'American College of Obstetricians and Gynecologists, de l'International Stillbirth Alliance Collaborative for Improving Classification of Perinatal Deaths, du Royal College of Obstetricians and Gynaecologists, des Queensland Clinical Guidelines et du Reproductive Care Program of Nova Scotia. Offrir les meilleurs conseils aux femmes quant aux causes possibles d'une mort fœtale et de leurs incidences sur des grossesses subséquentes. Le comité de médecine fœto-maternelle et le comité de pratique clinique – obstétrique de la Société des obstétriciens et gynécologues du Canada ont analysé et évalué les données probantes obtenues. La qualité des données et des recommandations a été déterminée à l'aide des critères d’évaluation des données du Groupe d'étude canadien sur les soins de santé préventifs. 1Il y a lieu d'utiliser un protocole pour enquêter sur la cause possible d'une mort fœtale (II-2A). 2Il convient de réaliser un bilan diagnostic après une mortinaissance en fonction des caractéristiques cliniques précises de chaque cas (II-2A). 3Il faut informer les parents du fait qu'aucune cause précise n'est déterminée dans près de la moitié des cas de mortinaissance (II-2B). 4Il y a lieu de recommander l'examen du cordon ombilical et du placenta, l'autopsie et l’évaluation cytogénétique à tous les parents, sans égard à leur héritage culturel, pour tenter d'expliquer la cause de la mort fœtale (II-2B). 5L'autopsie ne peut pas être réalisée sans le consentement éclairé des parents (III-A). 6Dans les cas où les parents ne consentent pas à l'autopsie, il y a lieu d'offrir un examen post mortem minimalement invasif au moyen de l'imagerie par résonance magnétique, lorsque disponible, combinée à un prélèvement histologique moins effractif que l'autopsie (III-B). Guideline No. 394-Stillbirth InvestigationJournal of Obstetrics and Gynaecology Canada Vol. 42Issue 1PreviewTo provide an investigation protocol to help health care providers determine the cause of a fetal death. Full-Text PDF

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.

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, 0.19mg/dL; 95% CI, 0.003 to 0.38mg/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.

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.

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.

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 werevitamin D,pregnancy,randomized controlled trials, andoffspring 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.

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.

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. (C) 2018 Elsevier B.V. All rights reserved.