Annie Ouellet

Prediction of adverse maternal outcomes in pre-eclampsia: development and validation of the fullPIERS model

BACKGROUND Pre-eclampsia is a leading cause of maternal deaths. These deaths mainly result from eclampsia, uncontrolled hypertension, or systemic inflammation. We developed and validated the fullPIERS model with the aim of identifying the risk of fatal or life-threatening complications in women with pre-eclampsia within 48 h of hospital admission for the disorder. METHODS We developed and internally validated the fullPIERS model in a prospective, multicentre study in women who were admitted to tertiary obstetric centres with pre-eclampsia or who developed pre-eclampsia after admission. The outcome of interest was maternal mortality or other serious complications of pre-eclampsia. Routinely reported and informative variables were included in a stepwise backward elimination regression model to predict the adverse maternal outcome. We assessed performance using the area under the curve (AUC) of the receiver operating characteristic (ROC). Standard bootstrapping techniques were used to assess potential overfitting. FINDINGS 261 of 2023 women with pre-eclampsia had adverse outcomes at any time after hospital admission (106 [5%] within 48 h of admission). Predictors of adverse maternal outcome included gestational age, chest pain or dyspnoea, oxygen saturation, platelet count, and creatinine and aspartate transaminase concentrations. The fullPIERS model predicted adverse maternal outcomes within 48 h of study eligibility (AUC ROC 0·88, 95% CI 0·84-0·92). There was no significant overfitting. fullPIERS performed well (AUC ROC >0·7) up to 7 days after eligibility. INTERPRETATION The fullPIERS model identifies women at increased risk of adverse outcomes up to 7 days before complications arise and can thereby modify direct patient care (eg, timing of delivery, place of care), improve the design of clinical trials, and inform biomedical investigations related to pre-eclampsia. FUNDING Canadian Institutes of Health Research; UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development, and Research Training in Human Reproduction; Preeclampsia Foundation; International Federation of Obstetricians and Gynecologists; Michael Smith Foundation for Health Research; and Child and Family Research Institute.

Obesity in Pregnancy

OBJECTIVE To review the evidence and provide recommendations for the counselling and management of obese parturients. OUTCOMES Outcomes evaluated include the impact of maternal obesity on the provision of antenatal and intrapartum care, maternal morbidity and mortality, and perinatal morbidity and mortality. EVIDENCE Literature was retrieved through searches of Statistics Canada, Medline, and The Cochrane Library on the impact of obesity in pregnancy on antepartum and intrapartum care, maternal morbidity and mortality, obstetrical anaesthesia, and perinatal morbidity and mortality. Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. Searches were updated on a regular basis and incorporated in the guideline to April 2009. 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 Maternal Fetal Medicine and Clinical Practice Obstetric Committees of the 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 Implementation of the recommendations in this guideline should increase recognition of the issues clinicians need to be aware of when managing obese women in pregnancy, improve communication and consultation amongst the obstetrical care team, and encourage federal and provincial agencies to educate Canadians about the values of entering pregnancy with as healthy a weight as possible. RECOMMENDATIONS 1. Periodic health examinations and other appointments for gynaecologic care prior to pregnancy offer ideal opportunities to raise the issue of weight loss before conception. Women should be encouraged to enter pregnancy with a BMI < 30 kg/m(2), and ideally < 25 kg/m(2). (III-B). 2. BMI should be calculated from pre-pregnancy height and weight. Those with a pre-pregnancy BMI > 30 kg/m(2) are considered obese. This information can be helpful in counselling women about pregnancy risks associated with obesity. (II-2B). 3. Obese pregnant women should receive counselling about weight gain, nutrition, and food choices. (II-2B). 4. Obese women should be advised that they are at risk for medical complications such as cardiac disease, pulmonary disease, gestational hypertension, gestational diabetes, and obstructive sleep apnea. Regular exercise during pregnancy may help to reduce some of these risks. (II-2B). 5. Obese women should be advised that their fetus is at an increased risk of congenital abnormalities, and appropriate screening should be done. (II-2B). 6. Obstetric care providers should take BMI into consideration when arranging for fetal anatomic assessment in the second trimester. Anatomic assessment at 20 to 22 weeks may be a better choice for the obese pregnant patient. (II-2B). 7. Obese pregnant women have an increased risk of Caesarean section, and the success of vaginal birth after Caesarean section is decreased. (II-2B). 8. Antenatal consultation with an anaesthesiologist should be considered to review analgesic options and to ensure a plan is in place should a regional anaesthetic be chosen. (III-B). 9. The risk of venous thromboembolism for each obese woman should be evaluated. In some clinical situations, consideration for thromboprophylaxis should be individualized. (III-B).

Substance Use in Pregnancy

OBJECTIVE To improve awareness and knowledge of problematic substance use in pregnancy and to provide evidence-based recommendations for the management of this challenging clinical issue for all health care providers. OPTIONS This guideline reviews the use of screening tools, general approach to care, and recommendations for clinical management of problematic substance use in pregnancy. OUTCOMES Evidence-based recommendations for screening and management of problematic substance use during pregnancy and lactation. EVIDENCE Medline, PubMed, CINAHL, and The Cochrane Library were searched for articles published from 1950 using the following key words: substance-related disorders, mass screening, pregnancy complications, pregnancy, prenatal care, cocaine, cannabis, methadone, opioid, tobacco, nicotine, solvents, hallucinogens, and amphetamines. Results were initially restricted to systematic reviews and randomized control trials/controlled clinical trials. A subsequent search for observational studies was also conducted because there are few RCTs in this field of study. Articles were restricted to human studies published in English. Additional articles were located by hand searching through article reference lists. Searches were updated on a regular basis and incorporated in the guideline up to December 2009. Grey (unpublished) literature was also 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 quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on the Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table 1). BENEFITS, HARMS, AND COSTS This guideline is intended to increase the knowledge and comfort level of health care providers caring for pregnant women who have substance use disorders. Improved access to health care and assistance with appropriate addiction care leads to reduced health care costs and decreased maternal and neonatal morbidity and mortality. RECOMMENDATIONS 1. All pregnant women and women of childbearing age should be screened periodically for alcohol, tobacco, and prescription and illicit drug use. (III-A) 2. When testing for substance use is clinically indicated, urine drug screening is the preferred method. (II-2A) Informed consent should be obtained from the woman before maternal drug toxicology testing is ordered. (III-B) 3. Policies and legal requirements with respect to drug testing of newborns may vary by jurisdiction, and caregivers should be familiar with the regulations in their region. (III-A) 4. Health care providers should employ a flexible approach to the care of women who have substance use problems, and they should encourage the use of all available community resources. (II-2B) 5. Women should be counselled about the risks of periconception, antepartum, and postpartum drug use. (III-B) 6. Smoking cessation counselling should be considered as a first-line intervention for pregnant smokers. (I-A) Nicotine replacement therapy and/or pharmacotherapy can be considered if counselling is not successful. (I-A) 7. Methadone maintenance treatment should be standard of care for opioid-dependent women during pregnancy. (II-IA) Other slow-release opioid preparations may be considered if methadone is not available. (II-2B) 8. Opioid detoxification should be reserved for selected women because of the high risk of relapse to opioids. (II-2B) 9. Opiate-dependent women should be informed that neonates exposed to heroin, prescription opioids, methadone, or buprenorphine during pregnancy are monitored closely for symptoms and signs of neonatal withdrawal (neonatal abstinence syndrome). (II-2B) Hospitals providing obstetric care should develop a protocol for assessment and management of neonates exposed to opiates during pregnancy. (III-B) 10. Antenatal planning for intrapartum and postpartum analgesia may be offered for all women in consultation with appropriate health care providers. (III-B) 11. The risks and benefits of breastfeeding should be weighed on an individual basis because methadone maintenance therapy is not a contraindication to breastfeeding. (II-3B).

The Use of Magnetic Resonance Imaging in the Obstetric Patient

OBJECTIVE To review the biological effects and safety of magnetic resonance imaging (MRI) in the obstetric patient and to review procedural issues, indications, and contraindications for obstetrical MRI. OUTCOMES This guideline is intended to reassure patients and clinicians of the safety of MRI in pregnancy and to provide a framework for its use. EVIDENCE Published literature was retrieved through searches of PubMed or Medline in 2013 using controlled vocabulary and key words (e.g., MRI, safety, pregnancy). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English and in French. There were no date restrictions. Searches were updated on a regular basis and incorporated in the guideline to July 2013. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies. VALUES The quality of evidence in 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 This article is intended to reassure obstetric care providers that if used in an appropriate manner without the use of contrast agents, MRI in the obstetrical patient is safe for mother and fetus in the second and third trimesters. Because obstetrical MRI is expensive and has limited availability in Canada, this clinical guideline is intended to encourage the judicious use of this resource. SUMMARY STATEMENTS: 1. Fetal magnetic resonance imaging is safe at 3.0 tesla or less during the second and third trimesters. (II-2) 2. It is safe to continue breastfeeding after receiving a gadolinium contrast agent. (III) RECOMMENDATIONS: 1. Use of magnetic resonance imaging during the first trimester of pregnancy should be restricted to maternal indications for which the information is considered clinically imperative. Inadvertent exposure to magnetic resonance imaging during the first trimester has not been associated with any long-term sequelae and should not raise clinical concern. (III-C) 2. Gadolinium contrast may be used in pregnant women when the benefits outweigh the potential risks. (III-C).

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.

Cytomegalovirus Infection in Pregnancy

OBJECTIVES To review the principles of prenatal diagnosis of congenital cytomegalovirus (CMV) infection and to describe the outcomes of the affected pregnancies. OUTCOMES Effective management of fetal infection following primary and secondary maternal CMV infection during pregnancy. Neonatal signs include intrauterine growth restriction (IUGR), microcephaly, hepatosplenomegaly, petechiae, jaundice, chorioretinitis, thrombocytopenia and anemia, and long-term sequelae consist of sensorineural hearing loss, mental retardation, delay of psychomotor development, and visual impairment. These guidelines provide a framework for diagnosis and management of suspected CMV infections. EVIDENCE Medline was searched for articles published in English from 1966 to 2009, using appropriate controlled vocabulary (congenital CMV infection) and key words (intrauterine growth restriction, microcephaly). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated into the guideline. 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. RECOMMENDATIONS The quality of evidence reported in this document has been assessed using the evaluation of evidence criteria in the Report of the Canadian Task Force on Preventive Health Care (Table 1). 1. Diagnosis of primary maternal cytomegalovirus (CMV) infection in pregnancy should be based on de-novo appearance of virus-specific IgG in the serum of a pregnant woman who was previously seronegative, or on detection of specific IgM antibody associated with low IgG avidity. (II-2A) 2. In case of primary maternal infection, parents should be informed about a 30% to 40% risk for intrauterine transmission and fetal infection, and a risk of 20% to 25% for development of sequelae postnatally if the fetus is infected. (II-2A) 3. The prenatal diagnosis of fetal CMV infection should be based on amniocentesis, which should be done at least 7 weeks after presumed time of maternal infection and after 21 weeks of gestation. This interval is important because it takes 5 to 7 weeks following fetal infection and subsequent replication of the virus in the kidney for a detectable quantity of the virus to be secreted to the amniotic fluid. (II-2A) 4. The diagnosis of secondary infection should be based on a significant rise of IgG antibody titre with or without the presence of IgM and high IgG avidity. In cases of proven secondary infection, amniocentesis may be considered, but the risk-benefit ratio is different because of the low transmission rate. (III-C) 5. Following a diagnosis of fetal CMV infection, serial ultrasound examinations should be performed every 2 to 4 weeks to detect sonographic abnormalities, which may aid in determining the prognosis of the fetus, although it is important to be aware that the absence of sonographic findings does not guarantee a normal outcome. (II-2B) 6. Quantitative determination of CMV DNA in the amniotic fluid may assist in predicting the fetal outcome. (II-3B) 7. Routine screening of pregnant women for CMV by serology testing is currently not recommended. (III-B) 8. Serologic testing for CMV may be considered for women who develop influenza-like illness during pregnancy or following detection of sonographic findings suggestive of CMV infection. (III-B) 9. Seronegative health care and child care workers may be offered serologic monitoring during pregnancy. Monitoring may also be considered for seronegative pregnant women who have a young child in day care. (III-B).

Potential biomarkers of preeclampsia: inverse correlation between hydrogen peroxide and nitric oxide early in maternal circulation and at term in placenta of women with preeclampsia.

Preeclampsia (PE) is a pregnancy-specific disease that has been associated with future cardiovascular disease for the mother and her child. The etiology of PE is unclear but oxidative stress seems to play a major role in endothelial dysfunction and permanent systemic vasoconstriction shown in PE. Hydrogen peroxide (H(2)O(2)), a terminal metabolite of the cellular oxidative stress cascade, is also revealed as a component of oxidative ischemia/reperfusion stress in placenta. We were the first to show an increase in the levels of H(2)O(2) in the serum of preeclamptic women at term. H(2)O(2) is already known to reduce the production of NO by increasing the metabolism of arginases. The objective of this study was to investigate a possible correlation between nitric oxide (NO), a potent vasodilator, and H(2)O(2) throughout pregnancy. Thus, we simultaneously assessed the levels of NO and H(2)O(2) in the serum of normal and preeclamptic women at 10-15 and 37-40 weeks of pregnancy, and in placentas at delivery. Our findings showed an inverse correlation between increased levels of H(2)O(2) and decreased levels of NO early in maternal circulation and at term in placenta. This relationship is confirmed by our in vitro experiments which demonstrate that H(2)O(2) inhibits NO synthesis of cytotrophoblasts. In conclusion, our findings highlight an inverse correlation between H(2)O(2) and NO early in maternal circulation and in placenta of women with preeclampsia, paving the way for further studies examining the potential use of NO and H(2)O(2) as biomarkers in the prediction of preeclampsia.

Vaginal delivery of breech presentation

To review the physiology of breech birth; to discern the risks and benefits of a trial of labour versus planned Caesarean section; and to recommend to obstetricians, family physicians, midwives, obstetrical nurses, anaesthesiologists, pediatricians, and other health care providers selection criteria, intrapartum management parameters, and delivery techniques for a trial of vaginal breech birth.

The Use of Progesterone for Prevention of Preterm Birth

OBJECTIVE To introduce new information on the use of progesterone to prevent premature labour and to provide guidance to obstetrical caregivers who counsel women on the merits of this choice OPTIONS This discussion is limited to progesterone therapy for prevention of preterm labour (PTL) in women at increased risk of PTL. EVIDENCE A search of both Medline and the Cochrane Library identified the most relevant medical evidence. This document represents an abstraction of the evidence rather than a methodological review. The level of evidence and quality of recommendations are described using the criteria and classifications of the Canadian Task Force on Preventive Health Care (Table 1). VALUES This update is the consensus of the Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC). BENEFITS, HARMS, AND COSTS Counselling the patient at increased risk for PTL should include consideration of the potential benefits of progesterone use and our lack of/limited knowledge of many neonatal outcomes and optimal dosing.

Ultrasonographic Cervical Length Assessment in Predicting Preterm Birth in Singleton Pregnancies

OBJECTIVES To review (1) the use of ultrasonographic-derived cervical length measurement in predicting preterm birth and (2) interventions associated with a short cervical length. OUTCOMES Reduction in rates of prematurity and/or better identification of those at risk, as well as possible prevention of unnecessary interventions. EVIDENCE Published literature was retrieved through searches of PubMed and The Cochrane Library up to December 2009, using appropriate controlled vocabulary and key words (preterm labour, ultrasound, cervix, incompetent cervix, transvaginal, transperineal, cervical length, fibronectin). Results were restricted to general and systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. There were no date or language restrictions. 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 and this guideline were reviewed by the Diagnostic Imaging Committee and the Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada, and the recommendations were made according to the guidelines developed by The Canadian Task Force on Preventive Health Care (Table 1). BENEFITS, HARMS, AND COSTS Preterm birth is a leading cause of perinatal morbidity and mortality. Use of the ultrasonographic technique reviewed in this guideline may help identify women at risk of preterm birth and, in some circumstances, lead to interventions that may reduce the rate of preterm birth. SPONSORS The Society of Obstetricians and Gynaecologists of Canada.