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

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).

Resume Objectifs Fournir un protocole d'investigation pour aider les fournisseurs de soins de sante a determiner la cause d'une mort fœtale. Options Une attention particuliere a ete portee aux protocoles d'investigation sur la mort fœtale disponibles au Canada et dans d'autres pays a l'heure actuelle. Resultats Determiner les causes possibles d'une mortinaissance et leur incidence sur les grossesses subsequentes. Donnees probantes Afin de retenir des articles relatifs a l'etiologie de la mort fœtale, des recherches ont ete effectuees dans les bases de donnees PubMed (juin 2006 a 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 subsequentes. Methodes de validation Le comite de medecine fœto-maternelle et le comite de pratique clinique – obstetrique de la Societe des obstetriciens et gynecologues du Canada ont analyse et evalue les donnees probantes obtenues. La qualite des donnees et des recommandations a ete determinee a l'aide des criteres d'evaluation des donnees du Groupe d'etude canadien sur les soins de sante preventifs. RECOMMANDATIONS 1Il y a lieu d'utiliser un protocole pour enqueter sur la cause possible d'une mort fœtale (II-2A). 2Il convient de realiser un bilan diagnostic apres une mortinaissance en fonction des caracteristiques cliniques precises de chaque cas (II-2A). 3Il faut informer les parents du fait qu'aucune cause precise n'est determinee dans pres de la moitie des cas de mortinaissance (II-2B). 4Il y a lieu de recommander l'examen du cordon ombilical et du placenta, l'autopsie et l'evaluation cytogenetique a tous les parents, sans egard a leur heritage culturel, pour tenter d'expliquer la cause de la mort fœtale (II-2B). 5L'autopsie ne peut pas etre realisee sans le consentement eclaire des parents (III-A). 6Dans les cas ou les parents ne consentent pas a l'autopsie, il y a lieu d'offrir un examen post mortem minimalement invasif au moyen de l'imagerie par resonance magnetique, lorsque disponible, combinee a un prelevement histologique moins effractif que l'autopsie (III-B).

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.

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 as...

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.

To provide an investigation protocol to help health care providers determine the cause of a fetal death.Consideration has been given to protocols for the investigation of fetal death that are currently available in Canada and in other countries.Identification of possible causes of stillbirth and their relationship to future pregnancies.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.To provide better advice for women regarding possible causes of fetal death and implications for future pregnancies.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.

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.

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 versus45 mm in the 2011 European guidelines.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).21/27 women had a vaginal delivery. The caesarean section rate was 23.8% and 16.7% in women with diameter40 mm and 40-45 mm respectively (p-value = 1), and perinatal outcome was similar across groups. Two women with a prepregnancy aortic root diameter40 mm developed an acute type B dissection during the third trimester. Both had a family history of aortic dissection.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.

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.

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.

Hypertensive disorders are the most common medical complication of pregnancy. As such, a large part of antenatal care is dedicated to the detection of pre-eclampsia, the most dangerous of the hypertensive disorders. The highlights of this chapter include progress in the use of out-of-office blood pressure measurement as an adjunct to office blood pressure measurement, pre-eclampsia defined as proteinuria or relevant end-organ dysfunction, antihypertensive therapy for severe and non-severe hypertension and post-partum follow-up to mitigate the increased cardiovascular risk associated with any of the hypertensive disorders of pregnancy.

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.

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.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 (IUGR5th percentile), Doppler anomalies of the umbilical artery and early onset IUGR (in the second trimester) of the growth restricted twin.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.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.

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.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.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.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 as34 or37 weeks' gestational age. Until the advent of optimal preventive strategies, close obstetric surveillance of twin pregnancies is warranted.

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 Quebec, 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.

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 betwe...

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.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.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, p0.0001). 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.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.

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.

Preeclampsia (PE) is characterized by maternal hypertension, proteinuria, oedema and, in 30% of cases, by intrauterine growth retardation. Causes are still unknown; however, epidemiological and clinical studies have suggested alterations in maternal calcium metabolism. We suggested that in PE, calcium transport by the syncytiotrophoblast (ST) is disturbed. From total placental tissues, we studied the expression of: calcium channels (TRPV5, TRPV6 [transient receptor potential vanilloid]), calcium binding proteins (CaBP-9K, CaBP-28K), plasma membrane calcium ATPase (PMCA)1,2,3,4 pumps, ATP synthase, genes implicated in Ca2+ release [inositol-1,4,5-triphosphate receptor (IP3R)1,2,3; Ryanodine receptor (RyR)1,2,3] and replenishment (SERCA1,2,3 [sarcoendoplasmic reticulum Ca2+ ATPases]) from endoplasmic reticulum, channels implicated in mitochondrial Ca2+ accumulation (VDAC1,2,3 [voltage-dependent anion channels]) and a marker of oxidative stress (hOGG1 [Human 8-oxoguanine-DNA glycosylase 1]), as well as the influence of these variations on calcium transport in primary ST cultures. The mRNA and protein levels were thereby examined by real-time PCR and Western blot analysis, respectively, in two different groups of pregnant women with similar gestational age: a normal group (n= 16) and a PE group (n= 8), diagnosed by a clinician. Our study showed a significant decrease in calcium transport by the ST cultured from preeclamptic placentas. We found a significant (P < 0.05) decrease in mRNA levels of TRPV5, TRPV6, CaBP-9K, CaBP-28K, PMCA1, PMCA4, ATP synthase, IP3R1, IP3R2, RyR1, RyR2 and RyR3 in PE group compared to normal one. We also noted a significant decrease in protein levels of TRPV5, TRPV6, CaBP-9K, CaBP-28K and PMCA1/4 in PE group. In contrast, SERCA1, SERCA2, SERCA3, VDAC3 and hOGG1 mRNA expressions were significantly increased in PE placentas. Calcium homeostasis and transport through placenta is compromised in preeclamptic pregnancies and it appears to be affected by a lack of ATP and an excess of oxidative stress.

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.

Objective To determine if the discrete myocardial diastolic dysfunction documented previously in the recipient twin during the early stages of twin–twin transfusion syndrome (TTTS) has any repercussion on flow velocities through the ductus venosus (DV) and to investigate if this could allow early differentiation between TTTS and selective intrauterine growth restriction (IUGR). Methods Two groups of monochorionic twin pregnancies with growth discordance between twins were reviewed retrospectively. Group I was composed of fetuses in Stages I and II of TTTS; laser or amnioreduction was not performed in any instance. Group II twin pairs each included one fetus with IUGR due to placental circulatory insufficiency. Intertwin differences (smaller minus larger fetus) were analyzed for myocardial performance index of the right ventricle (MPI-RV) and for time variables in the DV. Results There were 38 pairs of monochorionic twins (24 TTTS and 14 IUGR) in this study. In the TTTS group, the donors had a significantly lower MPI-RV (0.419 ± 0.18 vs. 0.596 ± 0.17, F(1, 19df) = 24.017, P < 0.001), a significantly longer total ventricular filling time (150.9 ± 25.6 ms vs. 124.0 ± 22.6 ms; F(1, 21df) = 19.631, P < 0.001) and a significantly longer early filling time (118.9 ± 22.9 ms vs. 92.6 ± 18.9 ms, F(1, 21df) = 28.419, P < 0.001) than had the recipient. None of these three differences was present in the IUGR group. Probability studies revealed that cut-off values of 12.75 for intertwin differences in total filling time and 8.5 for intertwin differences in early filling time had sensitivities of 71% and 92%, respectively. The false-positive rates were 23% and 15%, respectively, for the early diagnosis of TTTS. Conclusion In monochorionic twin pregnancies, shortening of the ventricular filling time in the recipient twin indicates diastolic myocardial dysfunction occurring early in the pathophysiology of TTTS. This early interwin difference in myocardial function is not found in pregnancies with IUGR in one twin due to placental circulatory insufficiency, allowing early differentiation between TTTS and selective IUGR. Copyright © 2007 ISUOG. Published by John Wiley & Sons, Ltd.

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.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.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%; P0.001). 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.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.

Resume Objectif Fournir un protocole d'enquete pour aider les fournisseurs de soins de sante a determiner la cause d'une mort fœtale. Options Nous avons pris en consideration les protocoles d'enquete sur les morts fœtales qui sont actuellement disponibles au Canada et dans d'autres pays. Issues dentification des causes possibles de mortinaissance et leur relation avec les futures grossesses. Resultats Des articles associes a l'etiologie de la mort fœtale ont ete recenses au moyen d'une recherche menee dans MEDLINE (de janvier 1993 a decembre 2004), la Cochrane Library et des protocoles d'enquete issus du American College of Obstetricians and Gynecologists , du Alberta Medical Association Committee on Reproductive Care et du Centers for Disease Control and Prevention National Center for Health Statistics . Avantages Offrir de meilleurs conseils aux femmes au sujet des causes possibles de mort fœtale et des implications en ce qui concerne les futures grossesses. Recommandations Un protocole d'enquete devrait etre utilise pour chercher a mettre au jour la cause d'une mort fœtale. (II-B) Validation Les resultats obtenus ont ete analyses et evalues par le comite de medecine fœto-maternelle et le comite de pratique clinique - obstetrique de la Societe des obstetriciens et gynecologues du Canada. Le niveau des resultats et la qualite des recommandations ont ete decrits au moyen des criteres d'evaluation des resultats du Groupe d'etude canadien sur l'examen medical periodique. Commanditaire La Societe des obstetriciens et gynecologues du Canada.

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 MEDLINE (January 1993 to December 2004), the Cochrane Library, and investigation protocols from the American College of Obstetricians and Gynecologists, the Alberta Medical Association Committee on Reproductive Care, and the Centers for Disease Control and Prevention National Center for Health Statistics. Benefits To provide better advice for women regarding possible causes of fetal death and implications for future pregnancies. Recommendation A protocol should be used to investigate the possible cause of a fetal death. (Il-B) 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 the Periodic Health Examination. Sponsor The Society of Obstetricians and Gynaecologists of Canada.

Maternofetal transport of l-carnitine, a molecule that shuttles long-chain fatty acids to the mitochondria for oxidation, is thought to be important in preparing the fetus for its lipid-rich postnatal milk diet. Using brush-border membrane (BBM) vesicles from human term placentas, we showed that l-carnitine uptake was sodium and temperature dependent, showed high affinity for carnitine (apparent Km= 11.09 ± 1.32 μM; Vmax= 41.75 ± 0.94 pmol·mg protein−1·min−1), and was unchanged over the pH range from 5.5 to 8.5. l-Carnitine uptake was inhibited in BBM vesicles by valproate, verapamil, tetraethylammonium, and pyrilamine and by structural analogs of l-carnitine, including d-carnitine, acetyl-d,l-carnitine, and propionyl-, butyryl-, octanoyl-, isovaleryl-, and palmitoyl-l-carnitine. Western blot analysis revealed that OCTN2, a high-affinity, Na+-dependent carnitine transporter, was present in placental BBM but not in isolated basal plasma membrane vesicles. The reported properties of OCTN2 resemble those observed for l-carnitine uptake in placental BBM vesicles, suggesting that OCTN2 may mediate most maternofetal carnitine transport in humans.

Objectives: (1) To determine the current use of treatment options for preterm labour and (2) to review the relative safety and efficacy of each class of tocolytic agent. Methods: MEDLINE and the Cochrane Library were searched using the terms "preterm delivery, " "preterm labour, " and "tocolysis" alone, and in combination with the terms "betamimetics, " "ritodrine, " "magnesium sulfate, " "calcium channel blockers, " "nifedipine, " "prostaglandin synthetase inhibitors, " "indomethacin, " "glyceryl trinitrate, " "nitroglycerin, " "oxytocin antagonists, " and "atosiban. " Randomized controlled trials (RCTs) that compared the effect of a tocolytic with a placebo or other tocolytic in women with preterm labour were selected. Trials were assessed according to Jadad's validated quality scale for assessing the quality of RCTs. Thirty-two RCTs retrieved met the inclusion criteria. Information not evident from RCTs was sought from non-randomized clinical trials, cohort studies, case control studies, case series, and case reports. Data from the Canadian Survey on Tocolytic Use was obtained directly from the Society of Obstetricians and Gynaecologists of Canada (SOGC). Results: The available evidence on the use of tocolytics to prolong pregnancy fails to show benefits in neonatal survival and reduced disability. This uncertainty of benefit makes the issue of fetal and maternal drug toxicity more important. There is great concern among SOGC members over the lack of effective and safe treatment options for the management of preterm labour. Conclusions: Further well-designed placebo-controlled trials are necessary to study the efficacy and safety of tocolytics in managing preterm labour

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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.

Objective: This executive summary presents in brief the current evidence assessed in the clinical practice guideline prepared by the Canadian Hypertensive Disorders of Pregnancy Working Group and published by Pregnancy Hypertension (. http://www.pregnancyhypertension.org/article/S2210-7789(14)00004-X/fulltext) to provide a reasonable approach to the diagnosis, evaluation, and treatment of the hypertensive disorders of pregnancy. Evidence: Published literature was retrieved through searches of Medline, CINAHL, and The Cochrane Library in March 2012 using appropriate controlled vocabulary (e.g., pregnancy, hypertension, pre-eclampsia, pregnancy toxemias) and key words (e.g., diagnosis, evaluation, classification, prediction, prevention, prognosis, treatment, postpartum follow-up). Results were restricted to systematic reviews, randomized control trials, controlled clinical trials, and observational studies published in French or English between January 2006 and February 2012. Searches were updated on a regular basis and incorporated in the guideline to September 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values: The quality of evidence in the guideline summarized here was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (. Table 1).

Background No reference values exist concerning the differences between cardio-circulatory variables of normal twin fetuses. The normal data could be useful in the identification of conditions causing opposite hemodynamic effects on each twin. Objective To establish the normal differences among cardio-circulatory parameters of twin fetuses during the second and third trimesters of gestation. Materials and methods Twenty-seven normal twin pregnancies were used in this longitudinal and prospective study. Doppler-echocardiographic investigations were performed every 2-3 weeks starting at an average of 23.11 ± 3.13 (mean ± standard deviation) weeks' gestation. At each visit, the following cardio-circulatory variables were evaluated: the cardio-thoracic ratio, the ventricular wall and septal thicknesses, end-diastolic and systolic diameters, ventricular fractional shortenings, velocity of circumferential fibre shortenings and left and right ventricular outputs. In addition the following measurements were made from Doppler recordings: through both aortic and pulmonary valve the acceleration and ejection times, the peak systolic velocities and the velocity time integrals; and through both mitral and tricuspid valves peak velocities of E and A waves and the E/A ratios. Finally the pulsatility index of the umbilical artery was also evaluated. Results There was no single variable where the intertwin difference changed with gestational age. No systematic difference between the smaller and larger twin could be demonstrated for any variables except for the cardio-thoracic ratio. Conclusion Reference tables should permit a comparative approach between the two twins in the investigation of life threatening complications such as twin-to‒twin transfusion syndrome. Copyright © 2000 International Society of Ultrasound in Obstetrics and Gynecology

Obstetric hemorrhage is still a potential cause of maternal mortality and morbidity. Angiographic embolization techniques have been described in cases of postcesarean bleeding, vaginal wall hematomas, cervical ectopic pregnancies, and postpartum bleeding to control persistent bleeding from pelvic vessels. We describe two cases of pregnancy complicated with placenta percreta. Balloon occlusion and embolization of the hypogastric arteries were performed during the cesarean section and hysterectomy, resulting in a remarkable reduction in intraoperative blood loss. Balloon occlusion and embolization of the internal iliac arteries significantly reduce intraoperative blood losses.

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.

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.

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.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 growth10th 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.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.In the twin model, intra-uterine growth restriction is associated with low-density lipoprotein oxidation without apparent dysregulation of inflammation biomarkers.Increased oxidized low-density lipoproteins are observed in growth restricted twins compared to their co-twins with normal growth at birth.

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.