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Introduction: Discriminating between placentally-mediated fetal growth restriction and constitutionally-small fetuses is a challenge in obstetric practice. Placental growth factor (PlGF), measurable in the maternal circulation, may have this discriminatory capacity. Methods: Plasma PlGF was measured in women presenting with suspected fetal growth restriction (FGR; ultrasound fetal abdominal circumference

Background Non-elective cervical cerclages are associated with significant perinatal complications. There is scant available information about what the predictors of these outcomes are, thus making counselling difficult. Objective To identify which factors predict delivery at or beyond 28, 34, and 37 weeks' gestation in women with emergency/rescue cervical cerclage. Methods We conducted a retrospective cohort study of nonelective cerclages over 10 years in our centre. We included women with singleton pregnancies, morphologically normal fetuses, and a cervix dilated to at least 1 cm. Our primary outcome was delivery at or beyond 28 weeks' gestation, and secondary outcomes consisted of delivery at or beyond 34 and 37 weeks' gestation. Descriptive statistical and logistic regression analyses were performed. Results We identified a total of 69 cases, and 47 met the inclusion criteria; 44.6% of these women delivered at or beyond 28 weeks' gestation. Membranes seen in the vagina on ultrasound and postcerclage preterm premature rupture of membranes decreased the chance of delivery at or beyond 28 weeks by 81.7% (OR 0.183; 95% CI 0.048 to 0.703) and 95% (OR 0.050; 95% CI 0.006 to 0.429), respectively. The same factors were predictive of deliveries at or beyond 34 and 37 weeks' gestation. Conclusion Membranes seen in the vagina on ultrasound and postcerclage pre-labour premature rupture of membranes were the strongest predictors of failure to reach 28 weeks' gestation. This information is of critical importance when counselling patients about non-elective cervical cerclage.

Objective To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of ‘less tight’ versus ‘tight’ control of pregnancy hypertension. Design Secondary analysis of CHIPS Trial cohort. Setting International randomised controlled trial (94 sites, 15 countries). Population or sample Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. Methods Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. Main outcome measures CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight

For hypertensive women in CHIPS (Control of Hypertension in Pregnancy Study), we assessed whether the maternal benefits of tight control could be achieved, while minimizing any potentially negative effect on fetal growth, by delaying initiation of antihypertensive therapy until later in pregnancy. For the 981 women with nonsevere, chronic or gestational hypertension randomized to less-tight (target diastolic blood pressure, 100 mm Hg), or tight (target, 85 mm Hg) control, we used mixed-effects logistic regression to examine whether the effect of less-tight (versus tight) control on major outcomes was dependent on gestational age at randomization, adjusting for baseline factors as in the primary analysis and including an interaction term between gestational age at randomization and treatment allocation. Gestational age was considered categorically (quartiles) and continuously (linear or quadratic form), and the optimal functional form selected to provide the best fit to the data based on the Akaike information criterion. Randomization before (but not after) 24 weeks to less-tight (versus tight) control was associated with fewer babies with birth weight P interaction =0.005), but more preterm birth ( P interaction =0.043), and no effect on perinatal death or high-level neonatal care >48 hours ( P interaction =0.354). For the mother, less-tight (versus tight) control was associated with more severe hypertension at all gestational ages but particularly so before 28 weeks ( P interaction =0.076). In women with nonsevere, chronic, or gestational hypertension, there seems to be no gestational age at which less-tight (versus tight) control is the preferred management strategy to optimize maternal or perinatal outcomes. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN71416914.

Placenta-mediated diseases (PMDs) including preeclampsia and fetal growth restriction are often characterized by shallow trophoblast invasion and incomplete spiral artery remodeling leading to impaired placental perfusion. In this context, umbilical artery (UA) Doppler can be used to detect high resistance to flow characteristic of very late-stage placental disease. We propose that evaluation of intraplacental villous artery (IPVA) resistance can provide earlier detection of increased resistance in placental flow. Seventy-five patients were recruited from the Ottawa Hospital. All had scans at 18 to 20, 28 and 34 weeks of gestation. IPVAs arising perpendicular to the chorionic plate in three regions (placental tips 4 cm away from cord insertion and within 1 cm from cord insertion) were sampled at each gestational age for resistance index (RI) and pulsatility index (PI). UA Doppler was also obtained from a free loop of cord. Pregnancy outcomes were collected from a chart review. Data were analyzed using SAS version 9.4 and standard statistic tests (mean±s.d., Student's t-test, mixed-effects modeling). A total of 53 patients completed the study. Of these, 38 had normal pregnancy outcomes (controls) and 15 (cases) developed PMD (preeclampsia, n=8 and low birth weight/intrauterine growth restriction, n=7). Mean birth weight in the study group was 2482.1±518.85 g. At 18 to 20, 28 and 34 weeks gestation, the mean IPVA resistance indices in the control group were 0.86±0.16, 0.81±0.12 and 0.71±0.12 for PI and 0.57±0.07, 0.55±0.06 and 0.49±0.06 for RI, respectively. However, in the cases developing PMDs, the PIs were 1.09±0.17, 0.95±0.21 and 0.78±0.07 and RIs 0.66±0.07, 0.60±0.07 and 0.54±0.04, respectively (P

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.

BACKGROUND\ud The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear.\ud METHODS\ud We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later.\ud RESULTS\ud Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (P

Background Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant's immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical trials registration NCT00553228.

I. Abstract Objective hepatitis C virus (HCV) is an increasingly important public health problem worldwide. Health care workers providing care to women of childbearing age are uniquely placed in their practices to identify a significant proportion of at-risk patients and to provide appropriate screening and counselling. The primary objective of this guideline is to provide accurate, current information to those offering reproductive care to women living with HCV. This document is also intended to raise awareness of HCV in both the medical and general populations. Options the areas of clinical practice considered in formulating this guideline are disease prevention, targeted screening of individuals at risk of contracting HCV, management of identified patients in the context of reproductive care, and the appropriate referral of patients to those with particular expertise. Outcomes implementation of these guidelines should facilitate identification of infected individuals. It should also result in improved physical and mental well-being for patients and their families and reduction in transmission rates. Evidence the literature between 1966 and 2000, including non- English language publications, was extensively searched utilizing Medline. A multidisciplinary group consisting of experts within the fields of obstetrics and gynaecology, infectious diseases, hepatology, and public health convened in Montreal in February 2000. The working group also included a patient and a representative from the Hepatitis C Society of Canada. The level of evidence for the recommendations has been determined using the criteria described by the Canadian Task Force on Periodic Health Examination. Benefits, harms and costs the public health benefits of increased identification of at-risk individuals, diagnosis, treatment, implementation of risk reduction behaviours, and reduced transmission rates, both on an individual and at the community level, are significant. However, it must be remembered that the diagnosis of a chronic disease may have far reaching effects for the individual patient and her family. Recommendations a)Screening •Universal screening for HCV is not recommended, although targeted screening should be offered to all women falling into any at-risk category. Testing should take place following adequate counselling and informed consent of the patient (III B). b)Preconception and early pregnancy care •Ideally, preconception or early pregnancy evaluation should include determination of risk of infection with hepatitis C, counselling, and testing as appropriate (III B). •Patients aware of their HCV positive diagnosis should be evaluated before embarking on pregnancy for complications that may compromise maternal health during pregnancy (III B). •Pregnancy is not generally contraindicated on grounds of HCV infection alone (Although it is contraindicated in the context of ribavirin therapy.) (III B). c)Care during pregnancy •There is a risk of vertical transmission which is greater if the woman is also infected with human immunodeficiency virus (HIV) (II-2 A). •Antenatal care will need to be tailored individually to meet the specific needs of the woman's medical and obstetrical condition, including the monitoring of liver function (II-2 A). •Alcohol should be avoided (II-2 A). •Immunization against hepatitis A and B should be provided as required (II-2 A). •Routine Caesarean section is not recommended as a specific intrapartum measure to reduce the risk of vertical transmission of hepatitis C (II-2 D). •Breastfeeding is not contraindicated (II-3 B). d)Care of infant •All infants born to HCV positive mothers should be evaluated for evidence of hepatitis C infection (III A). e)Contraception and hormone replacement therapy •Barrier methods should be recommended to those with multiple sexual partners (II-3 B). •The extent of liver disease should be carefully evaluated before considering the use of hormonal contraception or hormone replacement therapy (III B). f)Universal precautions •Universal precautions/routine practices and additional precautions are recommended in dealing with all patients for the protection of both health care worker and patient (II-2 A). Validation references were collected through Medline searches and comparison made to existing current guidelines for assessment of consistency. External reviewers expert in their field were also consulted.

Background Massive perivillous fibrin deposition (MPVFD) and chronic intervillositis (CI) are related rare pathological correlates of severe intrauterine growth restriction (IUGR) and fetal loss with high recurrence rates. No standard management has been established. Case A patient underwent termination of pregnancy at 21 weeks for severe early onset IUGR. Placental histology showed mixed CI with MPVFD. Several months later, the patient became pregnant and was managed with prednisone and aspirin (ASA) but miscarried at 16 weeks. Placental pathology showed MPVFD and focal CI. For two subsequent pregnancies, she was treated with intravenous immunoglobulin (IVIG), heparin, and ASA. Both pregnancies resulted in healthy near-term deliveries with normal placentas. Conclusion IVIG, heparin, and ASA can be an option in patients with recurrent pregnancy loss due to MPVFD and CI.

Background Emerging evidence from clinical and epidemiological studies suggests that dietary polyphenols play an important role in the prevention of chronic diseases, including cancer, cardiovascular disease, diabetes and neurodegenerative disorders. Although these beneficial health claims are supported by experimental data for many subpopulation groups, some studies purport that excessive polyphenol consumption may have negative health effects in other subpopulations. The ever-growing interest and public awareness surrounding the potential benefits of natural health products and polyphenols, in addition to their widespread availability and accessibility through nutritional supplements and fortified foods, has led to increased consumption throughout gestation. Therefore, understanding the implications of polyphenol intake on obstetrical health outcomes is of utmost importance with respect to safe consumption during pregnancy. Methods Using relevant keywords, a literature search was performed to gather information regarding polyphenol pharmacology and the molecular mechanisms by which polyphenols exert their biological effects. The primary focus of this paper is to understand the relevance of these findings in the context of reproductive physiology and medicine. Results Evidence from both in vitro experiments and in vivo studies using animals and humans demonstrates that polyphenols regulate key targets related to oxidative stress, inflammation and advanced glycation end products. Although the majority of these studies have been conducted in the context of chronic diseases, such as cancer and diabetes, several of the key targets influenced by polyphenols are also related to a variety of obstetrical complications, including pre-eclampsia, intrauterine growth restriction and preterm birth. Polyphenols have also been shown to influence fertility and sexual development, fetal health and the bioavailability of nutrients. Conclusions Further research leading to a thorough understanding of the physiological roles and potential clinical value that polyphenol consumption may play in pregnancy is urgently needed to help inform patient safety.

The quality of the intrauterine environment influences maternal-fetal health and also offspring predisposition to obesity and cardiometabolic disease later in life. Several determinants, including but not limited to pregravid obesity and excessive gestational weight gain, alter the developmental milieu, fetal growth, and child obesity risk. However, the role of sleep and its relationship to healthy pregnancy is not fully established. Given the host of psychosocial and physiological complications associated with childhood obesity, targeting the gestational period is purported to be an opportune time for preventive intervention. Many longitudinal studies suggest that short sleep duration is a risk factor for the development of impaired glycemia and obesity. However, there is a dearth of information concerning the role of sleep hygiene and its role in a healthy pregnancy. Reports note disrupted and poorer quality of sleep during gestation and highlight an association between reduced sleep and risk of gestational diabetes mellitus. Given the lack of well-designed human trials assessing the value of sleep and healthy pregnancy outcomes, this review summarizes current evidence which suggests that incorporating sleep recommendations and utilizing time management strategies that encourage a healthful night ’s sleep may improve the health of the mom and the baby.

Background: Over the past decade, the Ste20-like kinase SLK, has been implicated in several signaling processes. SLK repression has been shown to impair cell cycle kinetics and inhibit FAK-mediated cell migration. Here, using a gene trapped allele, we have generated mice expressing a truncated form of the SLK kinase. Results: Our results show that an SLK-LacZ fusion protein is expressed in embryonic stem cells and in embryos throughout development. We find that the SLK-LacZ fusion protein is less efficient at phosphorylating substrates resulting in reduced cell proliferation within the embryos and angiogenic defects in the placentae of the homozygous mutant animals at embryonic day (E) 12.5. This results in marked developmental defects and apoptotic lesions in the embryos by E14.5. Conclusions: Homozygotes expressing the SLK-LacZ fusion protein present with an embryonic lethal phenotype occurring between E12.5 and E14.5. Overall, we demonstrate a requirement for SLK kinase activity in the developing embryo and placenta. Developmental Dynamics 243:640–651, 2014. © 2013 Wiley Periodicals, Inc.

Maternal floor infarction is a relatively rare condition characterized clinically by severe early onset fetal growth restriction with features of uteroplacental insufficiency. It has a very high recurrence rate and carries a significant risk or fetal demise. Pathological characteristics include massive and diffuse fibrin deposition along the decidua basalis and the perivillous space of the basal plate. We present a case of recurrent maternal floor infarction and propose diagnostic clues as well as potential therapeutic options.

Objectives Health advocacy (HA) is a core competency in Canadian obstetrics and gynaecology postgraduate programs. Our objectives were to assess awareness and understanding of the health advocate role among trainees, their current HA training and exposure, and the desire and needs for future HA training. Methods An anonymous, cross-sectional, Internet-based, selfreported health advocacy questionnaire was distributed to Canadian obstetrics and gynaecology trainees. Descriptive analysis was conducted for all study variables. Chi-square tests, Cochran-Armitage trend test, and Fisher exact test were performed where appropriate. Results Most trainees (93.9% of respondents) were aware of the CanMEDS HA role and that it is a training objective (92.9%). Only 52.4% had clear objectives while 58.4% understood the role requirements. Most trainees (95.1% of respondents) felt HA was important to address during training. Only 30.4% had HA training, and just 36.3% felt their training needs were addressed. Training included teaching sessions (11.9%), clinical teaching (4.7%), and role modelling (4.7%). Although 82.9% of respondents had HA opportunities with patients, there were fewer opportunities at community (45.1%) and societal (30.0%) levels. Awareness of community groups and activities was low (28.6%), and few (20.0%) had participated in community advocacy programs during their residency. Incorporating advocacy activities into training was valued (80.0%). Many residents supported mandatory HA training (60.0%), more training time on HA experiences (66.3%), and HA experiences during protected time (71.3%). Conclusion Awareness of and interest in the HA role is high, but clear objectives and training are lacking or inadequate. A standardized curriculum would ensure health advocacy exposure and emphasize active participation in community and societal activities. Trainees support this training during protected time.

Maternal obesity is associated with increased risks of pregnancy complications. Excessive fat mass, common to obese women, has the potential to influence production and secretion of adipose tissue derived proteins called adipokines. The adipokine leptin is involved in the regulation of multiple aspects of maternal metabolic homeostasis. In addition, leptin has been shown to be important for placentation and maternal-fetal exchanges processes regulating growth and development. In later stages of a healthy pregnancy, central leptin resistance occurs to allow increased nutrient availability for the fetus. Disruption of the signaling capacity of leptin associated with obesity is emerging as a potential risk factor leading to pregnancy complications as a result of aberrant fuel partitioning in utero. In this review we discuss the influence of obesity on the roles of leptin and leptin resistance at the central and placental level.

Objective: To compare women's views about blood pressure (BP) control in CHIPS (Control of Hypertension In Pregnancy Study) (NCT01192412). Design: Quantitative and qualitative analysis of questionnaire responses. Setting: International randomised trial (94 sites, 15 countries). Population/sample: 911 (92.9%) women randomised to 'tight' (target diastolic blood pressure, 85 mmHg) or 'less tight' (target diastolic blood pressure, 100 mmHg) who completed questionnaires. Methods: A questionnaire was administered at similar to 6-12 weeks postpartum regarding post-discharge morbidity and views about trial participation. Questionnaires were administered by the site coordinator, and contact was made by phone, home or clinic visit; rarely, data was collected from medical records. Quantitative analyses were Chi-square or Fisher's exact test for categorical variables, mixed effects multinomial logistic regression to adjust for confounders, and p

Introduction For women with chronic or gestational hypertension in CHIPS (Control of Hypertension In Pregnancy Study, NCT01192412), we aimed to examine whether clinical predictors collected at randomization could predict adverse outcomes. Material and methods This was a planned, secondary analysis of data from the 987 women in the CHIPS Trial. Logistic regression was used to examine the impact of 19 candidate predictors on the probability of adverse perinatal (pregnancy loss or high level neonatal care for >48 h, or birthweight

PC4 or PCSK4 belongs to the 9-member superfamily of mammalian subtilases collectively called Proprotein Convertases or Proprotein Convertase Subtilisin/Kexins that convert inactive precursor proteins into their active mature forms by endoproteolytic cleavage. PC4-activity plays a crucial role in mammalian fertilization via activation of sperm surface proteins. PC4 knockout mice exhibit severely impaired male fertility due to premature sperm acrosome reaction. Regulation of sperm-PC4 activity during its storage and transport through epididymis is an important determinant for ultimate egg-binding and fertilizing capacities of sperms. Herein we show that epididymal serpin CRES (cystatin related epididymal spermatogenic) recombinant protein inhibits PC4 activity in vitro in a differential manner when measured against the fluorogenic substrate Boc- RVRR-MCA depending on its oligomeric state. Thus while CRES-dimer exhibits K(i) ∼8 μM, the corresponding monomer showed K(i)100 μM. Both forms also blocked PC4-mediated processing of human proIGF-2 in human placenta tropoblast cell line with dimer being more efficient. Using specific inhibitors and substrates, we also demonstrated the presence of PC4-like activity and CRES protein in varying levels in the fluids of various epididymal compartments. Our observations suggest a potential function of CRES as a regulator of PC4 in sperm-egg interaction and fertilization.

Sildenafil citrate therapy for severe early-onset intrauterine growth restriction. BJOG 2011;118:624-628. Currently, there is no effective therapy for severe early-onset intrauterine growth restriction (IUGR). Sildenafil citrate vasodilates the myometrial arteries isolated from women with IUGR-complicated pregnancies. Women were offered Sildenafil (25 mg three times daily until delivery) if their pregnancy was complicated by early-onset IUGR [abdominal circumference (AC)< 5th percentile] and either the gestational age was

Objective Misclassification of body mass index (BMI) by pregnant women could be a significant barrier to minimizing weight-related adverse pregnancy outcomes and improving the short- and long-term health of mother and child. The primary objective in this study was to determine the proportion of a group of pregnant women who were able to correctly classify BMI. Secondary objectives included assessing the direction of BMI misclassification and maternal knowledge of target gestational weight gain and obesity-associated pregnancy complications. Methods We designed a cross-sectional survey to assess misclassification of BMI and knowledge of obesity and pregnancy outcomes, and to provide information regarding the participants' sources of knowledge, their perception of appropriate weight gain in pregnancy, and basic demographic information. The questionnaire was completed by participants awaiting routine ultrasound assessment at between 11 and 24 weeks' gestation. Results Of 117 respondents, 30 (25.6%) were overweight (BMI 25 to 29.9) or obese (BMI ≥ 30.0). Obese or overweight women were significantly more likely to misclassify their BMI. Furthermore, they were significantly more likely to overestimate the minimum and maximum target gestational weight gains for their respective BMI classes. There were no differences between women in the various BMI categories with regard to their awareness of several common obesity-related pregnancy complications. Conclusion Misclassification of pre-pregnancy BMI is common, particularly among women carrying excess weight. Evaluation of pre-pregnancy BMI and education regarding appropriate gestational weight gain are logical initial steps for optimizing weight-related pregnancy outcomes.

Resume Objectif Analyser les resultats et formuler des recommandations sur le recours a l'antibioprophylaxie dans le cadre d'interventions obstetricales. Issues Parmi les issues evaluees, on trouve la necessite et l'efficacite du recours a des antibiotiques aux fins de la prevention des infections dans le cadre d'interventions obstetricales. Resultats La litterature publiee a ete recuperee par l'intermediaire de recherches menees dans Medline et The Cochrane Library au moyen de la rubrique « antibioprophylaxie dans le cadre d'interventions obstetricales ». Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles. Les recherches ont ete mises a jour de facon reguliere et les articles publies entre janvier 1978 et juin 2009 ont ete incorpores a la directive clinique. Les lignes directrices actuellement publiees par le American College of Obstetrics and Gynecology ont egalement ete incorporees a la directive clinique. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Valeurs Les resultats obtenus ont ete analyses et evalues par le comite sur les maladies infectieuses de la Societe des obstetriciens et gynecologues du Canada sous la gouverne des auteures principales, et les recommandations ont ete formulees conformement aux lignes directrices elaborees par le Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1). Avantages, desavantages et couts La mise en œuvre de la presente directive clinique devrait reduire les couts et les torts attribuables a l'administration d'antibiotiques lorsque celle-ci ne s'avere pas requise, ainsi que les torts attribuables a la non-administration d'antibiotiques lorsque ceux-ci pourraient s'averer benefiques. Declarations sommaires 1.Les donnees disponibles ne soutiennent pas le recours a l'antibioprophylaxie en vue d'attenuer la morbidite infectieuse a la suite d'un accouchement vaginal operatoire. (II-1) 2.Nous ne disposons pas de donnees suffisantes pour soutenir ou deconseiller le recours a l'antibioprophylaxie en vue d'attenuer la morbidite infectieuse dans les cas de retrait manuel du placenta. (III) 3.Nous ne disposons pas de donnees suffisantes pour soutenir ou deconseiller le recours a l'antibioprophylaxie au moment de la dilatation-curetage postpartum visant des produits de conception en retention. (III) 4.Les donnees disponibles ne soutiennent pas le recours a l'antibioprophylaxie en vue d'attenuer la morbidite infectieuse a la suite d'un cerclage planifie ou d'urgence. (II-3) Recommandations 1.Toutes les femmes qui subissent une cesarienne planifiee ou d'urgence devraient se voir administrer une antibioprophylaxie. (I-A) 2.Une dose unique d'une cephalosporine de premiere generation devrait constituer l'antibiotique a privilegier pour ce qui est des cesariennes. Lorsque la patiente presente une allergie a la penicilline, on peut avoir recours a la clindamycine ou a l'erythromycine. (I-A) 3.Dans le cas de la cesarienne, l'antibioprophylaxie devrait etre administree de 15 a 60 minutes avant l'incision de la peau. Aucune dose additionnelle n'est recommandee. (I-A) 4.Lorsqu'une intervention a abdomen ouvert est de longue duree (>3 heures) ou que la perte sanguine estimee est superieure a 1 500 ml, une dose additionnelle d'antibiotique prophylactique peut etre administree de 3 a 4 heures a la suite de la dose initiale. (III-L) 5.L'administration d'une antibioprophylaxie peut etre envisagee pour attenuer la morbidite infectieuse associee a la reparation d'une lesion perineale du troisieme ou du quatrieme degre. (I-B) 6.Chez les patientes massivement obeses (IMC > 35), il est possible d'envisager le doublement de la dose d'antibiotiques. (III-B) 7.L'administration d'antibiotiques aux seules fins de prevenir l'endocardite ne devrait pas etre mise en œuvre chez les patientes qui doivent subir une intervention obstetricale, quelle qu'en soit la nature. (III-E)

Intrauterine growth restriction (IUGR) and preeclampsia (PE) are leading causes of perinatal and maternal morbidity and mortality. Many studies have found association between low levels of insulin-like growth factor binding protein (IGFBP) proteases in the first trimester maternal circulation and the risk of subsequent development of PE and/or IUGR. These results are generally interpreted to reflect decreased production of the proteases by the placenta, leading to reduced proteolysis of IGFBPs and lower free levels of insulin-like growth factor (IGF), resulting in diminished feto-placental development. However, the association between low circulating levels of placental proteins early in pregnancy and the subsequent development of IUGR and/or PE could be due to low exchange in the placenta and not due to reduced production. In contrast, late in pregnancy, the circulating levels of these proteins and their expression in the placenta are often elevated in PE, which may reflect upregulation to compensate for abnormal placental development, that is an adaptive mechanism to increase IGFBP proteolysis, increase local IGF levels and promote feto-placental growth. Further research into the biological mechanisms underlying these associations will aid the identification of high-risk pregnancies and the development of therapeutic targets for diseases for which there are presently no preventative measures.

The NOTCH signaling pathway plays important roles in stem cell maintenance, cell-fate determination and differentiation during development. Following ligand binding, the cleaved NOTCH intracellular domain (NICD) interacts directly with the recombinant signal binding protein for immunoglobulin kappa J region (RBPJ) transcription factor and the resulting complex targets gene expression in the nucleus. To date, four human RBPJ isoforms have been described in Entrez Gene, varying in the first 5'coding exons. Using an improved protocol, we were able to further identify all four known and five novel RBPJ transcript variants in human amniotic fluid (AF) cells, a cell type known for its stem cell characteristics. In addition, we used human embryonal carcinoma (EC) NTera2/D1 (NT2) cells and NT2-derived neuron and astrocytes to compare the expression pattern of RBPJ transcripts. Further examination of RBPJ transcripts showed that the novel splice variants contain open reading frames in-frame with the known isoforms, suggesting that they can putatively generate similar function proteins. All known and novel RBPJ transcripts contain the putative nuclear localization signal (NLS), an important component of RBPJ-mediated gene regulation.

Resume Objectifs Analyser les principes du diagnostic prenatal de l'infection congenitale a cytomegalovirus (CMV) et decrire les issues des grossesses affectees. Issues Prise en charge efficace de l'infection fœtale a la suite d'une infection a CMV maternelle primaire et secondaire pendant la grossesse. Parmi les symptomes neonataux, on trouve le retard de croissance intra-uterin (RCIU), la microcephalie, l'hepatosplenomegalie, les petechies, l'ictere, la chorioretinite, la thrombocytopenie et l'anemie; parmi les sequelles a long terme, on trouve la surdite de perception, la deficience mentale, le retard du developpement psychomoteur et la deficience visuelle. La presente directive clinique offre un cadre pour le diagnostic et la prise en charge des infections a CMV soupconnees. Resultats Des recherches ont ete menees dans Medline en vue d'en tirer les articles publies en anglais, entre 1966 et 2009, au moyen d'un vocabulaire controle (infection congenitale a CMV) et de mots cles (retard de croissance intra-uterin, microcephalie) appropries. Les resultats ont ete restreints aux analyses systematiques, aux essais comparatifs randomises / essais cliniques comparatifs et aux etudes observationnelles. Les recherches ont ete regulierement mises a jour et leurs resultats ont ete incorpores a la directive clinique. La litterature grise (non publiee) a ete identifiee par l'intermediaire de recherches menees dans les sites Web d'organismes s'interessant a l'evaluation des technologies dans le domaine de la sante et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et aupres de societes de specialite medicale nationales et internationales. Recommandations La qualite des resultats signales dans le present document a ete evaluee au moyen des criteres d'evaluation des resultats decrits dans le rapport du Groupe d'etude canadien sur les soins de sante preventifs (Tableau 1). 1.Le diagnostic de l'infection a cytomegalovirus (CMV) maternelle primaire pendant la grossesse devrait etre fonde sur l'apparition de novo d'IgG propre au virus dans le serum d'une femme enceinte qui etait auparavant seronegative ou sur la detection d'anticorps IgM specifiques associes a de l'IgG de faible avidite. (II-2A) 2.En presence d'une infection maternelle primaire, les parents devraient etre avises du risque (de 30 % a 40 %) de transmission intra-uterine et d'infection fœtale, et du risque (de 20 % a 25 %) de voir apparaitre des sequelles postnatales lorsque le fœtus est infecte. (II-2A) 3.Le diagnostic prenatal de l'infection a CMV fœtale devrait etre fonde sur l'amniocentese, laquelle devrait etre menee au moins sept semaines a la suite du moment presume de l'infection maternelle et apres la 21 e semaine de gestation. Cet intervalle est important puisqu'il faut de cinq a sept semaines a la suite de l'infection fœtale et de la replication subsequente du virus dans le rein pour qu'une quantite detectable de virus soit secretee dans le liquide amniotique. (II-2A) 4.Le diagnostic de l'infection secondaire devrait etre fonde sur une hausse considerable du titre des anticorps IgM avec ou sans la presence d'anticorps IgM specifiques et en presence d'IgG de forte avidite. Dans les cas etablis d'infection secondaire, le recours a l'amniocentese peut etre envisage, mais le rapport risque–avantage est different en raison du faible taux de transmission. (III-C) 5.A la suite d'un diagnostic d'infection a CMV fœtale, des examens echographiques en serie devraient etre menes toutes les deux a quatre semaines afin de demeurer a l'affut des anomalies echographiques qui pourraient contribuer a la determination du pronostic fœtal; cependant, il est important d'etre conscient que l'absence de constatations echographiques ne garantit pas l'obtention d'une issue normale. (II-2B) 6.La determination quantitative de l'ADN de CMV dans le liquide amniotique peut contribuer a la prediction de l'issue fœtale. (II-3B) 7.Le depistage serologique systematique du CMV chez les femmes enceintes n'est actuellement pas recommande. (III-B) 8.Le depistage serologique du CMV peut etre envisage chez les femmes qui en viennent a presenter des symptomes grippaux pendant la grossesse ou a la suite de la detection de signes echographiques semblant indiquer une infection a CMV. (III-B) 9.Les femmes seronegatives œuvrant dans le domaine de la sante et des soins aux enfants peuvent se voir offrir un suivi serologique pendant la grossesse. Un suivi peut egalement etre envisage dans le cas des femmes enceintes seronegatives qui comptent un enfant en bas âge frequentant une garderie. (III-B)

Objective To review the evidence and provide recommendations on the use of antibiotics in preterm premature rupture of the membranes (PPROM). Outcomes Outcomes evaluated include the effect of antibiotic treatment on maternal infection, chorioamnionitis, and neonatal morbidity and mortality. Evidence Published literature was retrieved through searches of Medline, EMBASE, CINAHL, and The Cochrane Library, using appropriate controlled vocabulary and key words (PPROM, infection, and antibiotics). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and new material incorporated in the guideline to July 2008. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. Values The evidence obtained was reviewed and evaluated by the Infectious Diseases Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) under the leadership of the principal authors, and recommendations were made according to guidelines developed by the Canadian Task Force on Preventive Health Care. Benefits, Harms, and Costs Guideline implementation should assist the practitioner in developing an approach to the use of antibiotics in women with PPROM. Patients will benefit from appropriate management of this condition. Validation This guideline has been reviewed and approved by the Infectious Diseases Committee and the Maternal Fetal Medicine Committee of the SOGC, and approved by the Executive and Council of the SOGC. Sponsor The Society of Obstetricians and Gynaecologists of Canada. Recommendations 1.Following PPROM at 32 weeks' gestation, antibiotics should be administered to women who are not in labour in order to prolong pregnancy and to decrease maternal and neonatal morbidity (I-A). 2.The use of antibiotics should be gestational-age dependent. The evidence for benefit is greater at earlier gestational ages ( 3.For women with PPROM at >32 weeks' gestation, administration of antibiotics to prolong pregnancy is recommended if fetal lung maturity cannot be proven and/or delivery is not planned (I-A). 4.Antibiotic regimens may consist of an initial parenteral phase followed by an oral phase, or may consist of only an oral phase (I-A). 5.Antibiotics of choice are penicillins or macrolide antibiotics (erythromycin) in parenteral and/or oral forms. (I-A) In patients allergic to penicillin, macrolide antibiotics should be used alone (III-B). 6.The following two regimens may be used (the two regimens were used in the largest PPROM randomized controlled trials that showed a decrease in both maternal and neonatal morbidity): (1) ampicillin2g IV every 6 hours and erythromycin 250 mg IV every 6 hours for 48 hours followed by amoxicillin 250 mg orally every 8 hours and erythromycin 333 mg orally every 8 hours for 5 days (I-A); (2) erythromycin 250 mg orally every 6 hours for 10 days (I-A). 7.Amoxicillin/clavulanic acid should not be used because of an increased risk of necrotizing enterocolitis in neonates exposed to this antibiotic. Amoxicillin without clavulanic acid is safe (I-A). 8.Women presenting with PPROM should be screened for urinary tract infections, sexually transmitted infections, and group B streptococcus carriage, and treated with appropriate antibiotics if positive (II-2B).

Smoking during pregnancy has been shown to result in an increased risk of low birth weight. However, the mechanisms underlying this association are poorly understood. The insulin-like growth factor (IGF) system plays a critical role in the regulation of feto-placental growth and development, and abnormal processing of proIGF-II may alter its biological function. Our goal was to investigate the effects of exposure to nicotine on maternal, fetal, and neonatal IGF-II processing. Nulliparous female Wistar rats were randomly assigned to receive saline (vehicle) or nicotine bitartrate (1 mg x kg(-1) x d(- 1)). After mating, dams were euthanized at embryonic days 15, 18, and 21, and fetal body weight was recorded. Serum (fetal and maternal) was collected for determination of the IGF-II profile by Western blot analysis. Nicotine exposure prevented the decrease in maternal IGF-II processing seen in controls with advancing gestation. However, there was no influence of nicotine on fetal levels of IGF-II. Postnatally (postnatal day [PND] 21), pups exposed to nicotine in utero had decreased levels of big IGF-II. Our results show, for the first time, that nicotine exposure prevents the decrease of IGF-II processing in the maternal compartment. This may represent a compensatory mechanism allowing the mother to counteract the negative influence of nicotine on fetal growth and development. Our postnatal findings of suppressed IGF-II may help explain some of the long-term health complications seen in individuals exposed to smoking in utero.