Guideline No. 442: Fetal Growth Restriction: Screening, Diagnosis, and Management in Singleton Pregnancies.

OBJECTIVE: Fetal growth restriction is a common obstetrical complication that affects up to 10% of pregnancies in the general population and is most commonly due to underlying placental diseases. The purpose of this guideline is to provide summary statements and recommendations to support a clinical framework for effective screening, diagnosis, and management of pregnancies that are either at risk of or affected by fetal growth restriction. TARGET POPULATION: All pregnant patients with a singleton pregnancy. BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in this guideline should increase clinician competency to detect fetal growth restriction and provide appropriate interventions. EVIDENCE: Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library through to September 2022 using appropriate controlled vocabulary via MeSH terms (fetal growth retardation and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Grey 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. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations). INTENDED AUDIENCE: Obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, radiologists, and other health care providers who care for pregnant patients. TWEETABLE ABSTRACT: Updated guidelines on screening, diagnosis, and management of pregnancies at risk of or affected by FGR. SUMMARY STATEMENTS: RECOMMENDATIONS: Prediction of FGR Prevention of FGR Detection of FGR Investigations in Pregnancies with Suspected Fetal Growth Restriction Management of Early-Onset Fetal Growth Restriction Management of Late-Onset FGR Postpartum management and preconception counselling.

Directive clinique no 442 : Retard de croissance intra-utérin : Dépistage, diagnostic et prise en charge en contexte de grossesse monofœtale.

OBJECTIF: Le retard de croissance intra-utérin est une complication obstétricale fréquente qui touche jusqu'à 10 % des grossesses dans la population générale et qui est le plus souvent due à une pathologie placentaire sous-jacente. L'objectif de la présente directive clinique est de fournir des déclarations sommaires et des recommandations pour appuyer un protocole clinique de dépistage, diagnostic et prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. POPULATION CIBLE: Toutes les patientes enceintes menant une grossesse monofœtale. BéNéFICES, RISQUES ET COûTS: La mise en application des recommandations de la présente directive devrait améliorer la compétence des cliniciens quant à la détection du retard de croissance intra-utérin et à la réalisation des interventions indiquées. DONNéES PROBANTES: La littérature publiée a été colligée par des recherches effectuées jusqu'en septembre 2022 dans les bases de données PubMed, Medline, CINAHL et Cochrane Library en utilisant un vocabulaire contrôlé au moyen de termes MeSH pertinents (fetal growth retardation and small for gestational age) et de mots-clés (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Seuls les résultats de revues systématiques, d'essais cliniques randomisés ou comparatifs et d'études observationnelles ont été retenus. La littérature grise a été obtenue par des recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Obstétriciens, médecins de famille, infirmières, sages-femmes, spécialistes en médecine fœto-maternelle, radiologistes et autres professionnels de la santé qui prodiguent des soins aux patientes enceintes. RéSUMé POUR TWITTER: Mise à jour de la directive sur le dépistage, le diagnostic et la prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS: Prédiction du retard de croissance intra-utérin Prévention du retard de croissance intra-utérin Détection du retard de croissance intra-utérin Examens en cas de retard de croissance intra-utérin soupçonné Prise en charge du retard de croissance intra-utérin précoce Prise en charge du retard de croissance intra-utérin tardif Prise en charge du post-partum et consultations préconception.

How and when to recommend delivery of a growth-restricted fetus: A review.

Clinicians consider a range of variables when formulating decisions regarding the diagnosis, monitoring plan, and ultimately the decision to recommend the delivery of a growth-restricted fetus. The differential diagnosis of a pathological fetal growth pattern is initially considered via the history, a physical and laboratory examination of the pregnant person, as well as a comprehensive fetal ultrasound examination. These factors allow a broad distinction between pre-existing disease in the pregnant person, constitutionally small normal growth, placenta-mediated Fetal Growth Restriction (FGR), and intrinsic fetal disease. Most commonly, pathological growth restriction is mediated by underlying placental diseases, of which maternal vascular malperfusion is the most common, and often results in co-existent hypertension. A program of combined monitoring of the pregnant person and fetus, comprising hypertension assessment, and serial fetal ultrasound, including Doppler studies is then instituted, and may be combined with biochemical markers, such as Placental Growth Factor, for greater clinical precision. Recommendations on timing to deliver the growth-restricted fetus worldwide are converging, with similar guidance from clinical practice guidelines informed by high-quality Randomized Controlled Trials (RCTs) and large cohort studies. In most instances, it is reasonable to recommend delivery of all growth-restricted fetuses by approximately 38 weeks. Timing of delivery should take into consideration both short-term neonatal outcomes and long-term outcomes at school age. Mode of delivery is based on many factors, and induction of labor is a safe approach, especially after 34 weeks. Mechanical methods of induction may be preferred to pharmacologic methods, although both have a role and the choice of method is based on individualized assessment. Elective Cesarean birth thereby bypassing fetal stress during labor, is recommended in preterm growth-restricted fetuses with signs of adaptive fetal compromise, especially when ductus venosus flow is abnormal, or a contraction stress test is positive.

Suboptimal iron deficiency screening in pregnancy and the impact of socioeconomic status in a high-resource setting.

Iron deficiency (ID) anemia in pregnancy is associated with poor maternal and childhood outcomes, yet ferritin testing, the standard test for ID, is not considered part of routine prenatal bloodwork in Canada. We conducted a retrospective cohort study of 44 552 pregnant patients with prenatal testing at community laboratories in Ontario, Canada, to determine the prevalence of ferritin testing over 5 years. Secondary objectives were to determine the prevalence and severity of ID and to identify clinical and demographic variables that influence the likelihood of ID screening. A total of 59.4% of patients had a ferritin checked during pregnancy; 71.4% were ordered in the first trimester, when the risk of ID is lowest. Excluding patients with abnormally elevated ferritins, 25.2% were iron insufficient (30-44 µg/L) and 52.8% were iron deficient (≤29 µg/L) at least once in pregnancy. A total of 8.3% were anemic (hemoglobin <105 g/L). The proportion of anemic patients with a subsequent ferritin test in pregnancy ranged from 22% to 67% in the lowest and highest anemia severity categories, respectively. Lower annual household income was negatively associated with the odds of a ferritin test; compared with those in the fifth (ie, highest) income quintile, the odds of ferritin testing for patients in the first, second, and fourth quintiles were 0.83 (95% confidence interval [CI], 0.74-0.91), 0.82 (95% CI, 0.74-0.91), and 0.86 (95% CI, 0.77-0.97), respectively. These data highlight gaps in prenatal care and issues of health equity that warrant harmonization of obstetrical guidelines to recommend routine ferritin testing in pregnancy.

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

DESCRIPTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Development and implementation of a quality improvement toolkit, iron deficiency in pregnancy with maternal iron optimization (IRON MOM): A before-and-after study.

BACKGROUND: Iron deficiency (ID) in pregnancy is a common problem that can compromise both maternal and fetal health. Although daily iron supplementation is a simple and effective means of treating ID in pregnancy, ID and ID anemia (IDA) often go unrecognized and untreated due to lack of knowledge of their implications and competing clinical priorities. METHODS AND FINDINGS: In order to enhance screening and management of ID and IDA in pregnancy, we developed a novel quality-improvement toolkit: ID in pregnancy with maternal iron optimization (IRON MOM), implemented at St. Michael's Hospital in Toronto, Canada. It included clinical pathways for diagnosis and management, educational resources for clinicians and patients, templated laboratory requisitions, and standardized oral iron prescriptions. To assess the impact of IRON MOM, we retrospectively extracted laboratory data of all women seen in both the obstetrics clinic and the inpatient delivery ward settings from the electronic patient record (EPR) to compare measures pre- and post-implementation of the toolkit: a process measure of the rates of ferritin testing, and outcome measures of the proportion of women with an antenatal (predelivery) hemoglobin value below 100 g/L (anemia), the proportion of women who received a red blood cell (RBC) transfusion during pregnancy, and the proportion of women who received an RBC transfusion immediately following delivery or in the 8-week postpartum period. The pre-intervention period was from January 2012 to December 2016, and the post-intervention period was from January 2017 to December 2017. From the EPR, 1,292 and 2,400 ferritin tests and 16,603 and 3,282 antenatal hemoglobin results were extracted pre- and post-intervention, respectively. One year after implementation of IRON MOM, we found a 10-fold increase in the rate of ferritin testing in the obstetric clinics at our hospital and a lower risk of antenatal hemoglobin values below 100 g/L (pre-intervention 13.5% [95% confidence interval (CI) 13.0%-14.11%]; post-intervention 10.6% [95% CI 9.6%-11.7%], p < 0.0001). In addition, a significantly lower proportion of women received an RBC transfusion during their pregnancy (1.2% pre-intervention versus 0.8% post-intervention, p = 0.0499) or immediately following delivery and in the 8 weeks following (2.3% pre-intervention versus 1.6% post-intervention, p = 0.0214). Limitations of this study include the use of aggregate data extracted from the EPR, and lack of a control group. CONCLUSIONS: The introduction of a standardized toolkit including diagnostic and management pathways as well as other aids increased ferritin testing and decreased the incidence of anemia among women presenting for delivery at our site. This strategy also resulted in reduced proportions of women receiving RBC transfusion during pregnancy and in the first 8 weeks postpartum. The IRON MOM toolkit is a low-tech strategy that could be easily scaled to other settings.

Canadian Stroke Best Practice Consensus Statement: Acute Stroke Management during pregnancy.

The Canadian Stroke Best Practice Consensus Statement Acute Stroke Management during Pregnancy is the second of a two-part series devoted to stroke in pregnancy. The first part focused on the unique aspects of secondary stroke prevention in a woman with a prior history of stroke who is, or is planning to become, pregnant. This document focuses on the management of a woman who experiences an acute stroke during pregnancy. This consensus statement was developed in recognition of the need for a specifically tailored approach to the management of this group of patients in the absence of any broad-based, stroke-specific guidelines or consensus statements, which do not exist currently. The foundation for the development of this document was the concept that maternal health is vital for fetal well-being; therefore, management decisions should be based first on the confluence of two clinical considerations: (a) decisions that would be made if the patient wasn't pregnant and (b) decisions that would be made if the patient hadn't had a stroke, then nuanced as needed. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include initial emergency management, diagnostic imaging, acute stroke treatment, the management of hemorrhagic stroke, anesthetic management, post stroke management for women with a stroke in pregnancy, intrapartum considerations, and postpartum management. These statements are appropriate for healthcare professionals across all disciplines and system planners to ensure pregnant women who experience a stroke have timely access to both expert neurological and obstetric care.

Canadian stroke best practice consensus statement: Secondary stroke prevention during pregnancy.

The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy, is the first of a two-part series devoted to stroke in pregnancy. This document focuses on unique aspects of secondary stroke prevention in a woman with a prior history of stroke or transient ischemic attack who is, or is planning to become, pregnant. Although stroke is relatively rare in this cohort, several aspects of pregnancy can increase stroke risk during or immediately after pregnancy. The rationale for the development of this consensus statement is based on the premise that stroke in this group requires a specifically-tailored management approach. No other broad-based, stroke-specific guidelines or consensus statements exist currently. Underpinning the development of this document was the concept that maternal health is vital for fetal wellbeing; therefore, management decisions should be based on the confluence of two clinical considerations: (a) decisions that would be made if the patient was not pregnant and (b) decisions that would be made if the patient had not had a stroke. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include general management considerations for secondary stroke prevention, the use of antithrombotics, blood pressure management, lipid management, diabetes care, and management for specific ischemic stroke etiologies in pregnancy. The focus is on maternal and fetal health while minimizing risks of a recurrent stroke, through counseling, monitoring, and the safety of select pharmacotherapy. These statements are appropriate for health care professionals across all disciplines.

Episiotomy Technique and Management of Anal Sphincter Tears-A Survey of Clinical Practice and Education.

OBJECTIVE: To ascertain current techniques of episiotomy used by obstetrics and gynaecology faculty members and residents in an academic department and to determine the current management strategies for third and fourth degree tears. METHOD: A 14-question anonymous online survey was circulated to all faculty members and residents in the University of Toronto Department of Obstetrics and Gynaecology between October 2015 and March 2016. Results were analyzed descriptively or with Fisher exact test. RESULTS: The survey response rate was 65.5% (169/258) among 108 faculty members and 61 residents. A history of clinical teaching regarding episiotomy was reported by 87% of faculty members and 75.4% of residents. Right mediolateral episiotomy was the most frequently used method among faculty members (88.0%) and residents (95.1%). The majority of respondents indicated that they would use an end-to-end technique for repair in the labour and delivery room under regional anaesthesia. Prophylactic antibiotics were never prescribed by 18.5% of faculty members and 13.1% of residents for third or fourth degree tears. In analysis by type of training, respondents who had taken a workshop or formal class were significantly more likely to prescribe physiotherapy postpartum (P = 0.001). CONCLUSION: The most common reported method of learning episiotomy was clinical experience. A substantial number of responses differed from current SOGC guidelines for episiotomy technique and repair and management of anal sphincter injury. We propose developing a workshop and/or simulation-based method of instruction for episiotomy technique and repair.

Low Serum Vitamin B-12 Concentrations Are Prevalent in a Cohort of Pregnant Canadian Women.

BACKGROUND: Among Canadian women of reproductive age, 5% and 20% have serum vitamin B-12 concentrations indicative of deficiency (<148 pmol/L) and marginal status (148-220 pmol/L), respectively. Given the association between suboptimal vitamin B-12 and adverse pregnancy outcomes, an understanding of vitamin B-12 status during pregnancy, and factors that influence it, is required. OBJECTIVE: This prospective analysis from the PREFORM (PREnatal FOlic acid exposuRe on DNA Methylation in the newborn infant) study investigated 1) vitamin B-12 status in a cohort of Canadian pregnant women and their newborns, 2) the association of maternal dietary vitamin B-12 intake with maternal and cord blood concentrations of vitamin B-12 and its biomarkers, and 3) the association of fetal genetic polymorphisms with cord blood concentrations of vitamin B-12 and its biomarkers. METHODS: In pregnant Canadian women (n = 368; mean ± SD age: 32 ± 5 y), vitamin B-12 intakes were assessed in early (0-16 wk) and mid- to late (23-37 wk) pregnancy. Serum vitamin B-12 and plasma total homocysteine (tHcy) and methylmalonic acid (MMA) in maternal blood at 12-16 wk of pregnancy and at delivery (28-42 wk) and in cord blood were measured and compared by using regression analyses. The associations of 28 fetal genetic variants in vitamin B-12 metabolism and cord blood vitamin B-12, tHcy, and MMA concentrations were assessed by using regression analysis, with adjustment for multiple testing. RESULTS: A total of 17% and 38% of women had deficient and 35% and 43% had marginal serum vitamin B-12 concentrations at 12-16 wk of pregnancy and at delivery, respectively. Only 1.9-5.3% had elevated MMA (>271 nmol/L), and no women had elevated tHcy (>13 µmol/L). Maternal dietary vitamin B-12 intake during pregnancy was either weakly associated or not associated with maternal and cord blood vitamin B-12 (r(2) = 0.17-0.24, P < 0.0008), tHcy (P = NS) and MMA (r(2) = 0.05-0.11, P < 0.001). Fetal genetic polymorphisms were not associated with cord blood concentrations of vitamin B-12 and its biomarkers. CONCLUSIONS: Deficient and marginal serum vitamin B-12 concentrations are prevalent in Canadian pregnant women with the use of traditional cutoffs, despite supplement use. Given the growing interest among women to adhere to a vegetarian diet that may be lower in vitamin B-12, and vitamin B-12's importance in pregnancy, the functional ramifications of these observations need to be elucidated. This trial was registered at clinicaltrials.gov as NCT02244684.

High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood.

BACKGROUND: Mandatory fortification, prevalent supplement use, and public health guidelines recommending periconceptional supplementation have increased folic acid intakes in North American pregnant women. However, the effects of increased folic acid intakes during pregnancy on maternal and cord blood folate concentrations have not been well established. OBJECTIVES: In this prospective study, we determined maternal and cord blood concentrations of folate and unmetabolized folic acid (UMFA) in a cohort of pregnant Canadian women and their newborns and examined the effect of maternal intakes of folate and folic acid and fetal genetic variants in folate metabolism on folate status. DESIGN: Folate and folic acid intakes of 368 Canadian pregnant women were assessed in early (0-16 wk) and late (23-37 wk) pregnancy. Blood concentrations of folate and UMFA were measured with the use of immunoassays and liquid chromatography-mass spectrometry, respectively, in maternal samples in early pregnancy (12-16 wk), at delivery (28-42 wk), and in cord blood. Four fetal genetic variants of the 5,10-methylenetetrahydrofolate reductase (MTHFR) and dihydrofolate reductase (DHFR) genes were assessed for their association with cord blood concentrations of folate and UMFA. RESULTS: Geometric mean (95% CI) maternal red blood cell (RBC) folate concentrations were 2417 nmol/L (2362, 2472 nmol/L ) and 2793 nmol/L (2721, 2867 nmol/L ) in early pregnancy and at delivery, respectively. The mean (95% CI) cord RBC folate concentration was 2689 nmol/L (2614, 2765 nmol/L). UMFA was detectable in >90% of maternal and cord plasma samples. Although 3 fetal MTHFR and DHFR genetic variants had no effect, the fetal MTHFR 677TT genotype was associated with significantly lower cord serum (P = 0.03) and higher cord RBC (P = 0.02) folate concentrations than those of the wild type. CONCLUSIONS: Notwithstanding differences in assays, maternal and cord RBC folate and plasma UMFA concentrations were higher than previously reported values. Functional ramifications of high folate and UMFA concentrations in maternal and fetal circulation warrant additional investigation because an excess folate status may affect long-term health outcomes of the offspring. This study was registered at www.clinicaltrials.gov as NCT02244684.

Pregnant Canadian Women Achieve Recommended Intakes of One-Carbon Nutrients through Prenatal Supplementation but the Supplement Composition, Including Choline, Requires Reconsideration.

BACKGROUND: Folate, vitamin B-6, vitamin B-12, and choline are involved in one-carbon metabolism and play critical roles in pregnancy including prevention of birth defects and promotion of neurodevelopment. However, excessive intakes may adversely affect disease susceptibility in offspring. Intakes of these nutrients during pregnancy are not well characterized. OBJECTIVE: Our aim was to determine dietary and supplemental intakes and major dietary sources of one-carbon nutrients during pregnancy. METHODS: In pregnant women (n = 368) at ≤16 wk postconception, supplement use >30 d before pregnancy was assessed by maternal recall and supplement and dietary intakes in early (0-16 wk) and late pregnancy (23-37 wk) were assessed by food-frequency questionnaire. RESULTS: Preconception, 60.1% (95% CI: 55.8, 64.3) of women used B vitamin-containing supplements. This increased to 92.8% (95% CI: 89.6, 95.2) in early and 89.0% (95% CI: 85.0, 92.3) in late pregnancy. Median supplemental folic acid, vitamin B-12, and vitamin B-6 were 1000 µg/d, 2.6 µg/d, and 1.9 mg/d, respectively. Forty-one percent and 50% of women had dietary intakes of folate and vitamin B-6 less than the estimated average requirement (520 mg/d dietary folate equivalents and 1.6 mg/d, respectively). Eight-seven percent of women had choline intakes less than the Adequate Intake (450 mg/d). Dietary intakes did not change appreciably during pregnancy. Fruits and vegetables and fortified foods contributed ∼57% to total dietary folate intake. Fruits and vegetables contributed ∼32% to total dietary vitamin B-6 intake and dairy and egg products contributed ∼37% to total dietary vitamin B-12 intake. CONCLUSIONS: Vitamin supplements were an important source of one-carbon nutrients during pregnancy in our sample. Without supplements, many women would not have consumed quantities of folate and vitamin B-6 consistent with recommendations. Given the importance of choline in pregnancy, further research to consider inclusion in prenatal supplements is warranted. This trial was registered at clinicaltrials.gov as NCT02244684.

Maternal Choline Status, but Not Fetal Genotype, Influences Cord Plasma Choline Metabolite Concentrations.

BACKGROUND: Choline deficiency during pregnancy can lead to adverse birth outcomes, including impaired neurodevelopment and birth defects. Genetic variants of choline and one-carbon metabolism may also influence birth outcomes by altering plasma choline concentrations. The effects of maternal ad libitum choline intake during pregnancy and fetal genetic variants on maternal and cord concentrations of choline and its metabolites are unknown. OBJECTIVES: This prospective study sought to assess the effect of 1) maternal dietary choline intake on maternal and cord plasma concentrations of choline and its metabolites, and 2) fetal genetic polymorphisms on cord plasma concentrations. METHODS: The dietary choline intake of 368 pregnant Canadian women was assessed in early (0-16 wk) and late (23-37 wk) pregnancy with the use of a food frequency questionnaire. Plasma concentrations of free choline and its metabolites were measured in maternal samples at recruitment and delivery, and in the cord blood. Ten fetal genetic variants in choline and one-carbon metabolism were assessed for their association with cord plasma concentrations of free choline and its metabolites. RESULTS: Mean maternal plasma free choline, dimethylglycine, and trimethylamine N-oxide (TMAO) concentrations increased during pregnancy by 49%, 17%, and 13%, respectively (P < 0.005), whereas betaine concentrations decreased by 21% (P < 0.005). Cord plasma concentrations of free choline, betaine, dimethylglycine, and TMAO were 3.2, 2.0, 1.3, and 0.88 times corresponding maternal concentrations at delivery, respectively (all P < 0.005). Maternal plasma concentrations of betaine, dimethylglycine, and TMAO (r(2) = 0.19-0.51; P < 0.0001) at delivery were moderately strong, whereas maternal concentrations of free choline were not significant (r(2) = 0.12; P = 0.06), predictors of cord plasma concentrations of these metabolites. Neither maternal dietary intake nor fetal genetic variants predicted maternal or cord plasma concentrations of choline and its metabolites. CONCLUSION: These data collectively indicate that maternal choline status, but not fetal genotype, influences cord plasma concentrations of choline metabolites. This trial was registered at clinicaltrials.gov as NCT02244684.

Outcomes of pregnancy in women with hereditary hemorrhagic telangiectasia.

OBJECTIVE: To describe pregnancy outcomes in women with hereditary hemorrhagic telangiectasia (HHT). METHODS: This was a retrospective descriptive study of women with HHT (18-55 years of age) from the Toronto HHT Database using a telephone questionnaire regarding pregnancy, delivery, and neonatal outcomes. RESULTS: A total of 244 pregnancies were reported in 87 women with HHT. Miscarriages occurred in 20%. Hereditary hemorrhagic telangiectasia-related complications included minor hemoptysis during two pregnancies (1.1%) and hemothorax during four pregnancies (2.1%). One patient presenting with a hemothorax had presented during a previous pregnancy with a transient ischemic attack, most likely resulting from paradoxical emboli. One patient presented with an intracranial hemorrhage, and one patient presented with heart failure. These complications occurred in women previously unscreened and untreated for arteriovenous malformations. Other complications not clearly related to HHT were deep vein thrombosis (n=1), pulmonary embolism (n=1), myocardial infarction (n=1), and myocardial ischemia (n=1). Women noticed an increased frequency of epistaxis and development of new telangiectases during pregnancy. Epidural or spinal anesthesia was performed in 92 of 185 deliveries (50%) without complications. None of these women had undergone screening for spinal arteriovenous malformation before anesthesia. CONCLUSION: Women with HHT who have not been screened for arteriovenous malformations are at risk for serious pregnancy complications.

Intrauterine growth restriction: screening, diagnosis, and management.

BACKGROUND: Intrauterine growth restriction (IUGR) is an obstetrical complication, which by definition would screen in 10% of fetuses in the general population. The challenge is to identify the subset of pregnancies affected with pathological growth restriction in order to allow intervention that would decrease morbidity and mortality. OBJECTIVE: The purpose of this guideline is to provide summary statements and recommendations and to establish a framework for screening, diagnosis, and management of pregnancies affected with IUGR. METHODS: Affected pregnancies are compared with pregnancies in which the fetus is at an appropriate weight for its gestational age. History, physical examination, and laboratory investigations including biochemical markers and ultrasound characteristics of IUGR are reviewed, and a management strategy is suggested. EVIDENCE: Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library in January 2013 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. 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 this document was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care (Table). BENEFITS, HARMS, AND COSTS: Implementation of the recommendations in this guideline should increase clinician recognition of IUGR and guide intervention where appropriate. Optimal long-term follow-up of neonates diagnosed as IUGR may improve their long-term health.

Contexte : Le retard de croissance intra-utérin (RCIU) est une complication obstétricale qui, par définition, serait constatée par dépistage chez 10 % des fœtus au sein de la population générale. Le défi consiste à identifier le sous-ensemble des grossesses qui sont affectées par un retard de croissance pathologique, de façon à permettre la mise en œuvre d'une intervention qui atténuerait les taux de morbidité et de mortalité. Objectif : La présente directive clinique a pour objectif de fournir des déclarations sommaires et des recommandations, ainsi que d'établir un cadre pour le dépistage, le diagnostic et la prise en charge des grossesses affectées par un RCIU. Méthodes : Des grossesses affectées sont comparées à des grossesses dans le cadre desquelles le fœtus présente un poids convenant à son âge gestationnel. Les antécédents, l'examen physique et les analyses de laboratoire (y compris les marqueurs biochimiques et les caractéristiques échographiques du RCIU) sont analysées, et une stratégie de prise en charge est suggérée. Résultats : La littérature publiée en anglais a été récupérée par l'intermédiaire de recherches menées dans PubMed ou MEDLINE, CINAHL et The Cochrane Library en janvier 2013, au moyen d'un vocabulaire contrôlé faisant appel à des termes MeSH (« fetal growth restriction ¼ et « small for gestational age ¼) et à des mots clés (« fetal growth ¼, « restriction ¼, « growth retardation ¼, « IUGR ¼, « low birth weight ¼, « small for gestational age ¼) appropriés. Les résultats ont été restreints aux analyses systématiques, aux essais comparatifs randomisés / essais cliniques comparatifs et aux études observationnelles. La littérature grise (non publiée) a été identifiée par l'intermédiaire de recherches menées dans les sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, dans des registres d'essais cliniques et auprès de sociétés de spécialité médicale nationales et internationales. Valeurs : La qualité des résultats est évaluée au moyen des critères décrits dans le rapport du Groupe d'étude canadien sur les soins de santé préventifs (Tableau). Avantages, désavantages et coûts : La mise en œuvre des recommandations formulées aux présentes devraient accroître la reconnaissance du RCIU par les cliniciens et guider l'intervention, dans les cas où cela s'avère approprié. La mise en œuvre d'un suivi optimal à long terme des nouveau-nés présentant un diagnostic de RCIU pourrait améliorer leur santé à long terme. Déclarations sommaires 1. Dans le cas d'un fœtus in utero, l'hypotrophie fœtale se définit comme suit : un poids fœtal estimé inférieur au 10e percentile au moment de l'échographie. Ce diagnostic n'indique pas nécessairement la présence d'anomalies de croissance pathologiques et pourrait simplement décrire un fœtus se situant dans la partie inférieure de la plage normale. (III) 2. Par « retard de croissance intra-utérin ¼, on entend un fœtus présentant un poids fœtal estimé inférieur au 10e percentile au moment de l'échographie qui, en raison d'un processus pathologique, n'a pas atteint son potentiel de croissance biologiquement déterminé (III). L'estimation clinique du poids fœtal ou de la hauteur utérine compte une sensibilité et une spécificité faibles, et ne devrait pas être utilisée dans le cadre du diagnostic du retard de croissance intra-utérin. La présence de ce dernier devrait être prise en considération aux fins du diagnostic différentiel lorsque l'on constate que le fœtus présente une hypotrophie fœtale. (II-I) 3. Le dépistage efficace du retard de croissance intra-utérin nécessite une datation précise et comprend une analyse des antécédents menstruels de la mère, les données pertinentes en ce qui concerne le recours à des techniques de procréation assistée, ainsi qu'une échographie de datation menée au premier trimestre ou aux débuts du deuxième trimestre. (I) 4. Bien que la détermination de la hauteur utérine soit d'une valeur limitée dans le cadre des soins obstétricaux réguliers, elle demeure néanmoins le seul test de dépistage par examen physique disponible. (I) 5. La détermination du poids fœtal chez les fœtus se situant entre les 10e et 90e percentiles au moyen de la seule biométrie échographique compte un taux d'erreur d'au moins 10 % tout au long de la grossesse; toutefois, l'efficacité de l'établissement d'une estimation du poids fœtal est la même, que l'on ait recours à la mesure du périmètre abdominal seule ou conjointement avec celle des dimensions de la tête (diamètre bipariétal ou périmètre de la tête) et/ou de la longueur du fémur. (II-2) 6. La détermination de la symétrie ou de l'asymétrie du retard de croissance intra-utérin est moins importante sur le plan clinique que la tenue d'une réévaluation rigoureuse de l'anatomie fœtale et des études Doppler visant les artères utérine et ombilicale. (I) 7. Chez les femmes qui présentent des facteurs de risque en ce qui concerne le retard de croissance intra-utérin, la mise en œuvre d'un dépistage par étude Doppler de l'artère utérine à 19-23 semaines pourrait permettre l'identification des grossesses exposées à des risques de mortinaissance antepartum et d'accouchement préterme attribuables à un retard de croissance intra-utérin et à une pathologie placentaire. (II-2) 8. Dans le cadre des grossesses où un retard de croissance intra-utérin attribuable à une insuffisance vasculaire utéroplacentaire est diagnostiqué, la mise en œuvre d'une surveillance maternelle visant l'apparition possible d'une prééclampsie grave accompagnée de caractéristiques indésirables s'avère justifiée. (II-1) 9. Une fois mise en œuvre la surveillance d'un fœtus présentant un retard de croissance intra-utérin, les études Doppler de l'artère ombilicale et le score de profil biophysique peuvent être utilisés à titre de facteurs prédictifs à court terme du bien-être fœtal. (I) 10. En présence d'études Doppler anormales de l'artère ombilicale, une exploration approfondie du système circulatoire fœtal par examen Doppler de l'artère cérébrale moyenne, du canal d'Arantius et de la veine ombilicale peut être envisagée. (II-2) 11. Lorsque le fœtus présente un retard de croissance intra-utérin, la décision de procéder à une intervention obstétricale (y compris la césarienne, lorsque l'on constate une présentation ou une fréquence cardiaque fœtale anormale) est en grande partie fondée sur la viabilité fœtale, telle que déterminée par échographie. (II-2) 12. La mise en œuvre d'une surveillance maternelle visant l'apparition possible d'une prééclampsie est justifiée. (II-2) Recommandations 1. Les femmes devraient faire l'objet d'un dépistage visant les facteurs de risque cliniques du retard de croissance intra-utérin, et ce, au moyen d'une anamnèse exhaustive. (II-2B) 2. Les femmes devraient recevoir des conseils au sujet de l'abandon du tabagisme en tout temps au cours de la grossesse. (II-2A) 3. Les tests de dépistage de l'aneuploïdie au cours du premier et du deuxième trimestres pourraient constituer des tests utiles de la fonction placentaire. Lorsque deux résultats de test de dépistage se révèlent être anormaux, les fournisseurs de soins devraient savoir que le fœtus se trouve alors exposé à un risque accru de retard de croissance intra-utérin préterme et de mortinaissance connexe. (II-IA) 4. Lorsque la présence d'un retard de croissance intra-utérin est soupçonnée, la tenue d'autres évaluations peut contribuer à l'établissement d'un diagnostic. Lorsque cela s'avère possible, la tenue d'un examen échographique détaillé du placenta (à l'affût de signes indiquant la présence d'un petit placenta épaissi ou d'une morphologie anormale) et celle d'études Doppler de l'artère utérine devraient être envisagées à 19 - 23 semaines. Lorsque l'on ne dispose pas de moyens de procéder à un dépistage diagnostique, la mise en œuvre d'une surveillance plus étroite devrait être offerte. Une consultation en médecine fœto-maternelle peut être envisagée lorsque le placenta semble anormal au moment de l'échographie, particulièrement en présence d'un fœtus connaissant un retard de croissance et de résultats anormaux d'étude Doppler de l'artère utérine. En milieu rural, le fournisseur de soins doit décider si la patiente doit accoucher immédiatement ou si le transfert vers un centre tertiaire s'avère approprié. Une consultation téléphonique et le recours à la télémédecine pourraient être utiles. (II-2A) 5. Chez les femmes qui ne présentent pas de facteurs de risque en ce qui concerne le retard de croissance intra-utérin, la tenue d'un examen échographique exhaustif au troisième trimestre (comprenant un profil biophysique, une biométrie fœtale, le volume de liquide amniotique et des études Doppler de l'artère ombilicale) n'est pas recommandée. (II-2D) 6. L'administration d'aspirine à faible dose devrait être recommandée aux femmes qui présentent des antécédents de syndromes d'insuffisance placentaire (y compris le retard de croissance intra-utérin et la prééclampsie). Ce traitement devrait débuter entre 12 et 16 semaines de gestation, et se poursuivre jusqu'à 36 semaines. (I-A) 7. L'administration d'aspirine à faible dose devrait également être recommandée aux femmes qui présentent deux facteurs de risque établis ou plus pendant la grossesse, y compris (entre autres) l'hypertension prégestationnelle, l'obésité, un âge maternel > 40 ans, des antécédents quant au recours aux techniques de procréation assistée, le diabète sucré prégestationnel (type I ou II), une grossesse multiple, des antécédents de décollement placentaire et des antécédents d'infarctus placentaire. Ce traitement devrait débuter entre 12 et 16 semaines de gestation, et se poursuivre jusqu'à 36 semaines. (I-A) 8. La tenue d'études Doppler de l'artère ombilicale n'est pas recommandée à titre de test de dépistage systématique dans les cas degrossesse non compliquée. (I-E) 9. La tenue d'un examen échographique visant l'estimation du poids fœtal et la détermination du volume de liquide amniotique devrait être envisagée après 26 semaines, lorsque la hauteur utérine mesurée en centimètres présente une déviation de 3 ou plus par comparaison avec l'âge gestationnel déterminé en semaines, ou lorsque la hauteur utérine présente un plateau. (II-2B) 10. Lorsque le fœtus présente un poids fœtal estimé ou un périmètre abdominal < 10e percentile, la cause sous-jacente du retard de croissance intra-utérin pourrait être établie au moyen de la tenue d'un examen échographique plus poussé, comprenant une analyse détaillée de l'anatomie fœtale et de la morphologie placentaire, ainsi que des études Doppler des artères utérine et ombilicale. (II-2A) 11. Dans le cas des fœtus présentant un retard de croissance intra-utérin, la détermination du volume de liquide amniotique devrait être mise en œuvre pour contribuer au diagnostic différentiel du retard de croissance intra-utérin et accroître la précision du diagnostic d'insuffisance placentaire. (II-2B) 12. Une étude Doppler de l'artère ombilicale devrait être menée chez tous les fœtus dont le poids fœtal estimé ou le périmètre abdominal est < 10e percentile. (I-A) 13. Dans le cas des grossesses affectées par un retard de croissance intra-utérin, la tenue d'études Doppler de l'artère ombilicale après 24 semaines pourrait mener à une intervention permettant d'atténuer la mortalité périnatale et la morbidité périnatale grave attribuables au retard de croissance intra-utérin. (I-A) 14. Pour ce qui est des grossesses dans le cadre desquelles la présence d'un retard de croissance intra-utérin a été identifiée, la mise en œuvre d'un dépistage effractif visant à écarter la possibilité d'une aneuploïdie pourrait être offerte lorsque la présence d'anomalies fœtales est soupçonnée, que la présence de marqueurs faibles est constatée ou en l'absence de données permettant de soutenir la présence d'une insuffisance placentaire sous-jacente. (II-2A). 15. Chez les patientes qui présentent un retard de croissance intra-utérin, la mise en œuvre d'un dépistage maternel visant une étiologie infectieuse pourrait être envisagée. (II-2A) 16. En présence d'un diagnostic de retard de croissance intra-utérin, une surveillance devrait être mise en œuvre. La tenue en série (aux deux semaines) d'estimations du poids fœtal par échographie devrait être mise en œuvre, conjointement avec des études Doppler de l'artère ombilicale. Lorsque cela s'avère possible, une évaluation placentaire et d'autres études Doppler (comme celles qui visent l'artère cérébrale moyenne, la veine ombilicale et le canal d'Arantius) peuvent être menées. L'augmentation de la fréquence de la surveillance pourrait s'avérer requise. (II-2A) 17. Lorsque la croissance fœtale commence à être en plateau, que l'indice de liquide amniotique commence à décliner ou que le tonus fœtal ou les mouvements globaux sont diminués ou absents, une surveillance plus intensive (p. ex. de 2 à 3 fois par semaine) ou l'hospitalisation et la planification de l'accouchement s'avèrent requises. (II-2A) 18. En présence d'un retard de croissance intra-utérin, l'obtention de résultats anormaux à l'étude Doppler du cordon ombilical (p. ex. l'absence ou l'inversion du débit ventriculaire en fin de diastole) est inquiétante et nécessite la tenue d'une intervention et peut-être même celle de l'accouchement. (I-A) 19. La cardiotocographie (examen de réactivité fœtale) menée avant la naissance à titre de test visant à déterminer le bien-être fœtal ne devrait pas être utilisée de façon isolée pour assurer la surveillance des fœtus qui présentent un retard de croissance intra-utérin. (II-2E) 20. L'administration maternelle de corticostéroïdes s'avère indiquée en présence d'une possibilité importante de voir l'accouchement survenir avant 34 semaines de gestation, puisqu'elle pourrait exercer des effets positifs en ce qui concerne les études Doppler ombilicales. (I-A) 21. Lorsque l'accouchement n'était pas indiqué avant 37 semaines chez une patiente ayant reçu un diagnostic de retard de croissance intra-utérin, la décision de procéder à la mise en œuvre d'une prise en charge non interventionniste (s'accompagnant d'une surveillance fœtale et maternelle étroite) ou à l'accouchement devrait faire l'objet d'une discussion après 37 semaines. (I-A) 22. La détermination du site de l'accouchement planifié devrait tenir compte des installations et du savoir-faire disponibles dans chacun des établissements visés (y compris la présence d'obstétriciens, de pédiatres ou de néonatologistes [au besoin] et d'anesthésiologistes, et l'accès à la césarienne). (III-A).

A clinical tool for reducing central nervous system depression among neonates exposed to codeine through breast milk.

BACKGROUND: Neonates are commonly exposed to maternal codeine through breast milk. Central Nervous System (CNS) depression has been reported in up to 24% of nurslings following codeine exposure. In 2009, we developed guidelines to improve the safety of codeine use during breastfeeding based on previously established pharmacogenetic and clinical risk factors. The primary objective of this study was to prospectively evaluate the effectiveness of these guidelines in ensuring neonatal safety. METHODS AND FINDINGS: Women taking codeine for pain following caesarean section were given safety guidelines, including advice to use the lowest codeine dose for no longer than four days and to switch to a non-opioid when possible. Mothers provided a saliva sample for analysis of genes involved in opioid disposition, metabolism and response. A total of 238 consenting women participated. Neonatal sedation was reported in 2.1% (5/238) of breastfeeding women taking codeine according to our safety guidelines. This rate was eight fold lower than that reported in previous prospective studies. Women reporting sedated infants were taking codeine for a significantly longer period of time (4.80±2.59 days vs. 2.52±1.58 days, p = 0.0018). While following the codeine safety guidelines, mothers were less likely to supplement with formula, reported lower rates of sedation in themselves and breastfed more frequently throughout the day when compared to previously reported rates. Genotyping analysis of cytochrome p450 2D6 (CYP2D6), uridine-diphosphate glucuronosyltransferase (UGT) 2B7, p-glycoprotein (ABCB1), the mu-opioid receptor (OPRM1) and catechol-o-demethyltransferase (COMT) did not predict codeine response in breastfeeding mother/infant pairs when following the safety guidelines. CONCLUSIONS: The only cases of CNS depression occurred when the length of codeine use exceeded the guideline recommendations. Neonatal safety of codeine can be improved using evidence-based guidelines, even in those deemed by genetics to be at high risk for toxicity.

Expectant management compared with elective delivery at 37 weeks for gastroschisis.

OBJECTIVE: To estimate obstetric and neonatal outcomes after induction of labor at 37 weeks of gestation compared with expectant management in pregnancies complicated by fetal gastroschisis. METHODS: The management of 296 pregnancies involving fetal gastroschisis (1980-2011) was reviewed from a single perinatal center. Ultrasound surveillance and nonstress testing were performed every 2 weeks from 30 weeks of gestation, weekly from 34 weeks of gestation, and twice weekly after 35 weeks of gestation until delivery. Labor was induced if fetal well-being testing was abnormal and, since 1994, labor was routinely induced at 37 weeks of gestation. RESULTS: Of 153 pregnancies reaching 37 weeks of gestation, labor was induced in 77 (26%) and 76 (25.7%) were allowed to labor spontaneously. There were no significant differences in mean maternal age (22 years in both), parity (56% compared with 66% nulliparous), presence of other fetal anomalies (12% compared with 9%), cesarean delivery rate (20% in both), 5-minute Apgar score less than 7 (10% compared with 12%), meconium at birth (36% compared with 49%), or respiratory distress syndrome (16% compared with 7%) between the induced and expectantly managed groups. However, neonatal sepsis (25% compared with 42%; P=.02) and a composite outcome of neonatal death and bowel damage (necrosis, atresia, perforation, adhesion; 8% compared with 21%; P=.02) were more common in expectantly managed pregnancies. Moreover, time to oral feeds (-3.4 days), time on total parenteral nutrition (-6.2 days), and hospital stay (-6.7 days) were reduced when labor was induced. CONCLUSION: In fetuses with gastroschisis, induction of labor at 37 weeks of gestation was associated with reduced risks of sepsis, bowel damage, and neonatal death compared with pregnancies managed expectantly beyond 37 weeks of gestation. LEVEL OF EVIDENCE: II.

Screening, diagnosis, and management of intrauterine growth restriction.

OBJECTIVE: To provide comprehensive background knowledge relevant to the SOGC Maternal-Fetal Medicine Committee-approved guideline entitled "Intrauterine Growth Restriction: Screening, Diagnosis, and Management." METHODS: Publications in English were retrieved through searches of PubMed or Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary via MeSH terms (fetal growth restriction and small for gestational age) and any key words (fetal growth, restriction, growth retardation, intrauterine growth restriction [IUGR], low birth weight, small for gestational age). Results were restricted to systematic reviews, randomized controlled trials or controlled clinical trials, and high-quality prospective and retrospective observational studies. 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. RESULTS: Evidence obtained from at least one properly randomized controlled trial, Cochrane Reviews, and high quality cohort data have been combined to provide clinicians with evidence to optimize their practice for screening, diagnosis, and management of intrauterine growth restriction. CONCLUSION: Considerable advances have been made to improve clinicians' ability to screen, diagnose, and manage pregnancies with suspected IUGR more effectively, including several properly randomized controlled trials. Pregnancies with late-onset IUGR may be managed equally effectively by early delivery or delayed delivery (with increased surveillance) anticipating favourable outcomes. By contrast, many aspects of the management of early-onset IUGR require further clinical trials.