Robert Gagnon

Placental insufficiency and its consequences

Placental insufficiency is a process leading to progressive deterioration in placental function and a decrease in transplacental transfer of oxygen and nutrients to the fetus. The resulting fetal hypoxemia is the major stimulus involved in the reduction in fetal growth as an attempt to reduce metabolic demands by the growing fetus. Fetal growth restriction (FGR) is the second cause of perinatal death after prematurity and can complicate up to 6% of all pregnancies. It is becoming apparent that its occurrence has major impacts on the fetus and placenta with consequences on the cardiovascular, metabolic and neurological development up to adulthood. We are just starting to unveil some of the basic mechanisms involved in this complex adaptation that may lead to reprogramming of fetal organs development mostly the heart, pancreas, lungs and brain. It is becoming clear that future research is needed to develop strategies to improve antenatal detection of FGR, in addition to reduce the risk of abnormal neurodevelopment during childhood, and onset of common diseases in adulthood following pregnancies complicated with placental insufficiency.

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 Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice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).

Fetal endocrine responses to chronic placental embolization in the late-gestation ovine fetus * ** * **

OBJECTIVE The purpose of this study was to examine the effect of chronic fetal placental embolization on the fetal corticotropin, cortisol, and catecholamines concentrations and on myometrial contractility pattern. STUDY DESIGN Fourteen fetal sheep were studied (seven embolized, seven controls) for 10 days between 0.84 and 0.91 of gestation. Daily injections of nonradioactive microspheres were performed to decrease fetal arterial oxygen content by 30% to 35% of the preembolization value. Umbilical artery Doppler flow velocity waveforms were measured daily. RESULTS Chronic fetal placental embolization produced progressive fetal hypoxemia (p < 0.001) with changes in umbilical artery Doppler flow velocity waveforms indicative of a 25% increase in placental vascular resistance (p < 0.01). In response to chronic fetal hypoxemia there was a progressive increase in baseline fetal plasma norepinephrine concentration (p < 0.001). There was a transient fourfold to fivefold increase in baseline fetal plasma cortisol levels concomitant with a significant decrease in baseline immunoreactive corticotropin between days 7 and 9 of embolization (both p < 0.05), with a return to control values by day 10. There was a 57% increase in myometrial contracture frequency in the embolized group when compared with controls (p = 0.001). CONCLUSIONS During repetitive chronic placental damage that led to fetal hypoxemia, the fetal endocrine environment changed with time in a direction that would prevent the onset of premature activation of the hypothalamic-pituitary-adrenal axis and premature delivery.

Circulatory responses to prolonged hypoxemia in fetal sheep

Abstract Experiments were conducted in 11 chronically catheterized pregnant sheep to determine the distribution of blood flow within the fetus during prolonged (48 hours) hypoxemia secondary to the restriction of uterine blood flow. Uterine blood flow was mechanically restricted with a polytetrafluoroethylene vascular clamp placed around the maternal common internal iliac artery such that mean (± SEM) fetal arterial oxygen tension decreased from 23.4 ± 1.9 to 17.3 ± 0.8 mm Hg at 1 hour of hypoxemia and remained low for 48 hours. There was an initial increase in fetal arterial carbon dioxide pressure from 48.5 ± 0.9 mm Hg during the control period to 56.2 ± 2.3 mm Hg at 1 hour; this parameter subsequently returned to control values, whereas base excess showed a transient decrease. Fetal cerebral, myocardial, and adrenal blood flows were significantly increased at 1, 24, and 48 hours of hypoxemia. In contrast, there was no change in nuchal muscle or renal blood flows with hypoxemia of this magnitude. Cotyledonary blood flow increased transiently by 38% at 1 hour of hypoxemia, but was not changed from control at 24 and 48 hours. These experiments demonstrate that the sheep fetus is able to maintain the normal protective circulatory adjustments seen with acute hypoxemia for up to 48 hours in the absence of progressive metabolic acidemia.

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.

Guidelines for the Number of Embryos toTransfer Following In Vitro Fertilization

OBJECTIVE To review the effect of the number of embryos transferred on the outcome of in vitro fertilization (IVF), to provide guidelines on the number of embryos to transfer in IVF-embryo transfer (ET) in order to optimize healthy live births and minimize multiple pregnancies. OPTIONS Rates of live birth, clinical pregnancy, and multiple pregnancy or birth by number of embryos transferred are compared. OUTCOMES Clinical pregnancy, multiple pregnancy, and live birth rates. EVIDENCE The Cochrane Library and MEDLINE were searched for English language articles from 1990 to April 2006. Search terms included embryo transfer (ET), assisted reproduction, in vitro fertilization (IVF), ntracytoplasmic sperm injection (ICSI), multiple pregnancy, and multiple gestation. Additional references were identified through hand searches of bibliographies of identified articles. VALUES Available evidence was reviewed by the Reproductive Endocrinology and Infertility Committee and the Maternal-Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada and the Board of the Canadian Fertility and Andrology Society, and was qualified using the Evaluation of Evidence Guidelines developed by the Canadian Task Force on the Periodic Health Exam. BENEFITS, HARMS, AND COSTS This guideline is intended to minimize the occurrence of multifetal gestation, particularly high-order multiples (HOM), while maintaining acceptable overall pregnancy and live birth rates following IVF-ET.

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).

Fetal placental embolization in the late-gestation ovine fetus: Alterations in umbilical blood flow and fetal heart rate patterns

OBJECTIVE Our goal was to determine the effect of chronic and acute umbilical-placental embolization on placental hemodynamic and fetal heart rate patterns in relation to fetal oxygenation in the near-term ovine fetus. STUDY DESIGN Daily fetal placental embolization was performed during 10 days in 9 sheep fetuses until fetal arterial oxygen content decreased by approximately 30%. Nine control fetuses received saline solution. Mean and pulsatile umbilical blood flow, perfusion pressure, placental vascular resistance, fundamental impedance, pressure pulsatility index, and umbilical artery resistance index corrected to a fetal heart rate of 160 beats/min were measured. On day 10 both groups were acutely embolized until fetal arterial pH decreased to approximately 7.00. Fetal heart rate was measured with the Sonicaid System 8000 (Oxford Sonicaid, Oxford, United Kingdom). RESULTS Chronic fetal placental embolization was associated with a progressive reduction in umbilical blood flow (p < 0.00001) and fetal arterial oxygen content (p < 0.001) whereas fetal heart rate patterns remained unaltered. A chronic increase in umbilical artery resistance index corrected to a fetal heart rate of 160 beats/min could be entirely explained only if the changes in umbilical artery pressure pulsatility index and the fundamental impedance were taken into account, in addition to the changes observed in placental vascular resistance. During acute embolization leading to a 50% reduction in umbilical blood flow (p < 0.0002) and a three times increase in placental vascular resistance (p < 0.0001), the most consistent change in fetal heart rate patterns related to progressive metabolic acidosis was an 84% decrease in absolute acceleration frequency (p < 0.0001) whereas short-term fetal heart rate variability remained unaltered. CONCLUSION Changes in umbilical artery resistance index induced by chronic umbilical-placental embolization resulting in fetal hypoxemia occurred before any changes in fetal heart rate patterns were detectable. A decrease in the absolute acceleration frequency was the only component of fetal heart rate patterns related to progressive metabolic acidosis in the near-term ovine fetus.

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.