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Guideline Obstetrical complications associated with abnormal maternal serum markers analytes. 2008
Gagnon A, Wilson RD, Audibert F, Allen VM, Blight C, Brock JA, Désilets VA, Johnson JA, Langlois S, Summers A, Wyatt P, Anonymous00047. · Vancouver BC. · J Obstet Gynaecol Can. · Pubmed #19038077 No free full text.
Abstract: OBJECTIVE: To review the obstetrical outcomes associated with abnormally elevated or decreased level of one or more of the most frequently measured maternal serum marker analytes used in screening for aneuploidy. To provide guidance to facilitate the management of pregnancies that have abnormal levels of one of more markers and to assess the usefulness of these markers as a screening test. OPTIONS: Perinatal outcomes associated with abnormal levels of maternal serum markers analytes are compared with the outcomes of pregnancies with normal levels of the same analytes or the general population. EVIDENCE: The Cochrane Library and Medline were searched for English-language articles published from 1966 to February 2007, relating to maternal serum markers and perinatal outcomes. Search terms included PAPP-A (pregnancy associated plasma protein A), AFP (alphafetoprotein), hCG (human chorionic gonadotropin), estriol, unconjugated estriol, inhibin, inhibin-A, maternal serum screen, triple marker screen, quadruple screen, integrated prenatal screen, first trimester screen, and combined prenatal screen. All study types were reviewed. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Key individual studies on which the recommendations are based are referenced. Supporting data for each recommendation are summarized with evaluative comments and references. The evidence was evaluated using the guidelines developed by the Canadian Task Force on Preventive Health Care. VALUES: The evidence collected was reviewed by the Genetics Committee of the Society of Obstetricians and Gynaecologists of Canada. BENEFITS, HARMS, AND COSTS: The benefit expected from this guideline is to facilitate early detection of potential adverse pregnancy outcomes when risks are identified at the time of a maternal serum screen. It will help further stratification of risk and provide options for pregnancy management to minimize the impact of pregnancy complications. The potential harms resulting from such practice are associated with the so called false positive (i.e., uncomplicated pregnancies labelled at increased risk for adverse perinatal outcomes), the potential stress associated with such a label, and the investigations performed for surveillance in this situation. No cost-benefit analysis is available to assess costs and savings associated with this guideline. SUMMARY STATEMENTS: 1. An unexplained level of a maternal serum marker analyte is defined as an abnormal level after confirmation of gestational age by ultrasound and exclusion of maternal, fetal, or placental causes for the abnormal level. (III) 2. Abnormally elevated levels of serum markers are associated with adverse pregnancy outcomes in twin pregnancies, after correction for the number of fetuses. Spontaneous or planned mutifetal reductions may result in abnormal elevations of serum markers. (II-2) RECOMMENDATIONS: 1. In the first trimester, an unexplained low PAPP-A (< 0.4 MoM) and/or a low hCG (< 0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) In the second trimester, an unexplained elevation of maternal serum AFP (> 2.5 MoM), hCG (> 3.0 MoM), and/or inhibin-A (> or =2.0 MoM) or a decreased level of maternal serum AFP (< 0.25 MoM) and/or unconjugated estriol (< 0.5 MoM) are associated with an increased frequency of adverse obstetrical outcomes, and, at present, no specific protocol for treatment is available. (II-2A) 2. Pregnant woman with an unexplained elevated PAPP-A or hCG in the first trimester and an unexplained low hCG or inhibin-A and an unexplained elevated unconjugated estriol in the second trimester should receive normal antenatal care, as this pattern of analytes is not associated with adverse perinatal outcomes. (II-2A) 3. The combination of second or third trimester placenta previa and an unexplained elevated maternal serum AFP should increase the index of suspicion for placenta accreta, increta, or percreta. (II-2B) An assessment (ultrasound, MRI) of the placental-uterine interface should be performed. Abnormal invasion should be strongly suspected, and the planning of delivery location and technique should be done accordingly. (III-C) 4. A prenatal consultation with the medical genetics department is recommended for low unconjugated estriol levels (<0.3 MoM), as this analyte pattern can be associated with genetic conditions. (II-2B) 5. The clinical management protocol for identification of potential adverse obstetrical outcomes should be guided by one or more abnormal maternal serum marker analyte value rather than the false positive screening results for the trisomy 21 and/or the trisomy 18 screen. (II-2B) 6. Pregnant woman who are undergoing renal dialysis or who have had a renal transplant should be offered maternal serum screening, but interpretation of the result is difficult as the level of serum hCG is not reliable. (II-2A) 7. Abnormal maternal uterine artery Doppler in association with elevated maternal serum AFP, hCG, or inhibin-A or decreased PAPP-A identifies a group of women at greater risk of IUGR and gestational hypertension with proteinuria. Uterine artery Doppler measurements may be used in the evaluation of an unexplained abnormal level of either of these markers. (II-2B) 8. Further research is recommended to identify the best protocol for pregnancy management and surveillance in women identified at increased risk of adverse pregnancy outcomes based on an abnormality of a maternal serum screening analyte. (III-A) 9. In the absence of evidence supporting any specific surveillance protocol, an obstetrician should be consulted in order to establish a fetal surveillance plan specific to the increased obstetrical risks (maternal and fetal) identified. This plan may include enhanced patient education on signs and symptoms of the most common complications, increased frequency of antenatal visits, increased ultrasound (fetal growth, amniotic fluid levels), and fetal surveillance (biophysical profile, arterial and venous Doppler), and cervical length assessment. (III-A) 10. Limited information suggests that, in women with elevated hCG in the second trimester and/or abnormal uterine artery Doppler (at 22-24 weeks), low-dose aspirin (60-81 mg daily) is associated with higher birthweight and lower incidence of gestational hypertension with proteinuria. This therapy may be used in women who are at risk. (II-2B) 11. Further studies are recommended in order to assess the benefits of low-dose aspirin, low molecular weight heparin, or other therapeutic options in pregnancies determined to be at increased risk on the basis of an abnormal maternal serum screening analyte. (III-A) 12. Multiple maternal serum markers screening should not be used at present as a population-based screening method for adverse pregnancy outcomes (such as preeclampsia, placental abruption, and stillbirth) outside an established research protocol, as sensitivity is low, false positive rates are high, and no management protocol has been shown to clearly improve outcomes. (II-2D) When maternal serum screening is performed for the usual clinical indication (fetal aneuploidy and/or neural tube defect), abnormal analyte results can be utilized for the identification of pregnancies at risk and to direct their clinical management. (II-2B) Further studies are recommended to determine the optimal screening method for poor maternal and/or perinatal outcomes. (III-A).
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Guideline Pregnancy outcomes after assisted reproductive technology. 2006
Allen VM, Wilson RD, Cheung A, Anonymous00192, Anonymous00193. · Halifax, NS, Canada. · J Obstet Gynaecol Can. · Pubmed #16650361 No free full text.
Abstract: OBJECTIVE: To review the effect of assisted reproductive technology (ART) on perinatal outcomes, to provide guidelines to optimize obstetrical management and counselling of Canadian women using ART, and to identify areas specific to birth outcomes and ART requiring further research. OPTIONS: Perinatal outcomes of ART pregnancies in subfertile women are compared with those of spontaneously conceived pregnancies. Perinatal outcomes are compared between different types of ART. OUTCOMES: This guideline discusses the adverse outcomes that have been recorded in association with ART, including obstetrical complications, adverse perinatal outcomes, multiple gestations, structural congenital abnormalities, chromosomal abnormalities, imprinting disorders, and childhood cancer. EVIDENCE: The Cochrane Library and MEDLINE were searched for English-language articles from 1990 to February 2005, relating to assisted reproduction and perinatal outcomes. Search terms included assisted reproduction, assisted reproductive technology, ovulation induction, intracytoplasmic sperm injection (ICSI), embryo transfer, and in vitro fertilization (IVF). Additional publications were identified from the bibliographies of these articles as well as the Science Citation Index. Studies assessing gamete intrafallopian transfer (GIFT) and zygote intrafallopian transfer (ZIFT) were excluded since they are rarely used in Canada. All study types were reviewed. Randomized controlled trials were considered evidence of the highest quality, followed by cohort studies. Key studies and supporting data for each recommendation are summarized with evaluative comments and referenced. VALUES: The evidence collected was reviewed by the Genetics Committee and the Reproductive Endocrinology Infertility Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the Evaluation of Evidence Guidelines developed by the Canadian Task Force on the Periodic Health Examination. BENEFITS, HARMS, AND COSTS: The type and magnitude of benefits, harms, and costs expected for patients from guideline implementation. This guideline has been reviewed by the Genetics Committee and the Reproductive Endocrinology and Infertility Committee, and approved by the Executive and Council of the Society of Obstetricians and Gynaecologists of Canada and the Board of the Canadian Fertility and Andrology Society. RECOMMENDATIONS: 1. Spontaneous pregnancies in untreated infertile women may be at higher risk for obstetrical complications and perinatal mortality than spontaneous pregnancies in fertile women. Further research is required to clarify the contribution of infertility itself to adverse obstetrical and perinatal outcomes. (II-2A) 2. All men with severe oligozoospermia or azoospermia should be offered genetic/clinical counselling for informed consent and offered karyotyping for chromosomal abnormalities before attempting IVF-ICSI. They should be made aware of the availability of tests for Y chromosome microdeletion. Some patients may consider the option of donor insemination. (II-3B) 3. Couples exploring IVF-ICSI when the man has obstructive azoospermia should be offered genetic/clinical counselling for informed consent and offered genetic testing for alterations in genes associated with cystic fibrosis (CF) before attempting IVF-ICSI. (II-2A) 4. Pregnancies achieved by ovarian stimulation with gonadotropins and intrauterine insemination are at higher risk for perinatal complications, and close surveillance during pregnancy should be considered. It remains unclear if these increased risks are attributable to the underlying infertility, characteristics of the infertile couple, or use of assisted reproductive techniques. Multiple gestations remain a significant risk of gonadotropin treatment. (II-2A) 5. Pregnancies achieved by IVF with or without ICSI are at higher risk for obstetrical and perinatal complications than spontaneous pregnancies, and close surveillance during pregnancy should be considered. It remains unclear if these increased risks are attributable to the underlying infertility, characteristics of the infertile couple, or use of assisted reproductive techniques. (II-2A) 6. Women undergoing ART should be informed about the increased rate of obstetrical interventions such as induced labour and elective Caesarean delivery. (II-2A) 7. Couples suffering from infertility who are exploring treatment options should be made aware of the psychosocial implications of ART. Further research into the psychosocial impact of ART is needed. (II-2A) 8. Singleton pregnancies achieved by assisted reproduction are at higher risk than spontaneous pregnancies for adverse perinatal outcomes, including perinatal mortality, preterm delivery, and low birth weight, and close surveillance during pregnancy should be available as needed. (II-2A) 9. A significant risk of ART is multiple pregnancies. Infertile couples need to be informed of the increased risks of multifetal pregnancies. Although dichorionic twins are most common, the incidence of monochorionic twins is also increased. Risks of multiple pregnancies include higher rates of perinatal mortality, preterm birth, low birth weight, gestational hypertension, placental abruption, and placenta previa. Perinatal mortality in assisted conception twin pregnancies appears to be lower than in spontaneously conceived twin pregnancies. (II-2A) 10. When multifetal reduction is being considered for high-order multiple pregnancies, psychosocial counselling should be readily available. Careful surveillance for fetal growth problems should be undertaken after multifetal reduction. (II-2A) 11. To reduce the risks of multiple pregnancies associated with ART and to optimize pregnancy rates, national guidelines should be developed on the number of embryos replaced according to characteristics such as patient's age and grade of embryos. (II-2A) 12. Further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks to childhood and long-term growth and development associated with ART. (II-2A) 13. Discussion of options for prenatal screening for congenital structural abnormalities in pregnancies achieved by ART is recommended, including appropriate use of biochemical and sonographic screening. (II-2A) 14. Further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks of congenital abnormalities associated with ART. (II-2A) 15. Couples considering IVF-ICSI for male-factor infertility should receive information, and if necessary formal genetic counselling, about the increased risk of de novo chromosomal abnormalities (mainly sex chromosomal anomalies) associated with their condition. Prenatal diagnosis by chorionic villus sampling (CVS) or amniocentesis should be offered to these couples if they conceive. (II-2A) 16. Further epidemiologic and basic science research is needed to help determine the etiology and extent of the increased risks of chromosomal abnormalities associated with ART. (II-2A) 17. Discussion of options for prenatal screening and testing for aneuploidy in pregnancies achieved by ART, adapted for maternal age and number of fetuses, is recommended, including appropriate use of biochemical and sonographic screening. (II-2A) 18. The precise risks of imprinting and childhood cancer from ART remain unclear but cannot be ignored. Further clinical research, including long-term follow-up, is urgently required to evaluate the prevalence of imprinting disorders and cancers associated with ART. (II-2A) 19. The clinical application of preimplantation genetic diagnosis must balance the benefits of avoiding disease transmission with the medical risks and financial burden of in vitro fertilization. Further ethical discussion and clinical research is required to evaluate appropriate indications for preimplantation genetic diagnosis. (III-B).
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Clinical Conference Late first-trimester placental disruption and subsequent gestational hypertension/preeclampsia. 2005
Silver RK, Wilson RD, Philip J, Thom EA, Zachary JM, Mohide P, Mahoney MJ, Simpson JL, Platt LD, Pergament E, Hershey D, Filkins K, Johnson A, Wapner RJ, Jackson LG, Anonymous00167. · Evanston Hospital of Northwestern University Medical School, Evanston, Illinois 60201, USA. · Obstet Gynecol. · Pubmed #15738029 No free full text.
Abstract: OBJECTIVE: To evaluate the potential relationship between placental disruption in weeks 13 and 14 and the subsequent development of gestational hypertension or preeclampsia. METHODS: Using subjects recruited during a randomized trial funded by the National Institute of Child Health and Human Development, which compared early amniocentesis and late transabdominal chorionic villus sampling (CVS) in weeks 13 and 14, rates of gestational hypertension and preeclampsia were compared between cases with varying degrees of placental disruption. RESULTS: A total of 3,698 of 3,775 randomized subjects had cytogenetically normal pregnancies and were analyzed. A significantly higher rate of hypertension/preeclampsia was observed in the late CVS group (5.4%, n = 1,878) compared with the early amniocentesis cohort (3.5%, n = 1,820; P = .005). This difference persisted after controlling for maternal age, body mass index, parity, previous preterm delivery, smoking, and fetal gender. Early amniocentesis cases were further stratified on the basis of whether the placenta had been penetrated (n = 460) or not (n = 1,360). Risk of hypertensive complications was lowest if the placenta was not traversed (3.4%), greater with placental penetration (3.9%), and highest when the placenta was directly sampled during CVS (5.4%, P = .02). CONCLUSION: We hypothesize that focal disruption of the placenta at 13-14 weeks may increase the risk of hypertension/preeclampsia. These findings provide support for the theory that disturbances in early placentation lead subsequently to maternal hypertension.
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Clinical Conference Screening for fetal well-being in a high-risk pregnant population comparing the nonstress test with umbilical artery Doppler velocimetry: a randomized controlled clinical trial. 2003
Williams KP, Farquharson DF, Bebbington M, Dansereau J, Galerneau F, Wilson RD, Shaw D, Kent N. · Department of Obstetrics and Gynecology, Yale University School of Medicine, 333 Cedar Street, PO Box 208063, New Haven, CT 06520-8063, USA. · Am J Obstet Gynecol. · Pubmed #12748513 No free full text.
Abstract: OBJECTIVE: The purpose of this study was to evaluate the ability of two different modes of antepartum fetal testing to screen for the presence of peripartum morbidity, as measured by the cesarean delivery rate for fetal distress in labor. STUDY DESIGN: Over a 36-month period, all patients who were referred to the Fetal Assessment Unit at BC Women's Hospital because of a perceived increased fetal antepartum risk at a gestational age of > or =32 weeks of gestation were approached to participate in this study. Fetal surveillance of these women was allocated randomly to either umbilical artery Doppler ultrasound testing or nonstress testing as a screening test for fetal well-being. If either the umbilical artery Doppler testing or the nonstress testing was normal, patients were screened subsequently with the same technique, according to study protocol. When the Doppler study showed a systolic/diastolic ratio of >90th percentile or the nonstress testing was equivocal (ie, variable decelerations), an amniotic fluid index was performed, as an additional screening test. When the amniotic fluid index was abnormal (<5th percentile), induction and delivery were recommended. When the Doppler study showed absent or reversed diastolic blood flow or when the nonstress test result was abnormal, induction and delivery were recommended to the attending physician. Statistical comparisons between groups were performed with an unpaired t test for normally distributed continuous variables and chi(2) test for categoric variables. RESULTS: One thousand three hundred sixty patients were assigned randomly to groups in the study; 16 patients were lost to follow up. Six hundred forty-nine patients received Doppler testing and 691 received nonstress testing. The mean number of visits for the Doppler test and nonstress test groups was two versus two, respectively. The major indications for fetal assessment included postdates (43%), decreased fetal movement (22%), diabetes mellitus (11%), hypertension (10%), and intrauterine growth restriction (7%). The incidence of cesarean delivery for fetal distress was significantly lower in the Doppler group compared with the nonstress testing group (30 [4.6%] vs 60 [8.7%], respectively; P <.006). The greatest impact on the reduction in cesarean deliveries for fetal distress was seen in the subgroups in which the indication for testing was hypertension and suspected intrauterine growth restriction. CONCLUSION: Umbilical artery Doppler as a screening test for fetal well-being in a high-risk population was associated with a decreased incidence of cesarean delivery for fetal distress compared to the nonstress testing, with no increase in neonatal morbidity.
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Article The ex utero intrapartum therapy procedure for high-risk fetal lung lesions. 2005
Hedrick HL, Flake AW, Crombleholme TM, Howell LJ, Johnson MP, Wilson RD, Adzick NS. · The Center for Fetal Diagnosis and Treatment, The Children's Hospital of Philadelphia, Philadelphia, PA 19104-4399, USA. · J Pediatr Surg. · Pubmed #15991193 No free full text.
Abstract: BACKGROUND: Indications for the ex utero intrapartum therapy (EXIT) procedure have expanded to include any fetal anomaly in which resuscitation of the neonate may be compromised. METHODS: We reviewed the medical records of 9 patients after resection of lung lesions during the EXIT procedure. RESULTS: The mean gestational age at EXIT procedure was 35.4 weeks. All lung masses maintained large sizes late into gestation with mean mass volume/head circumference ratio of 2.5 at presentation and 2.2 at EXIT. Seven of 9 fetuses demonstrated hydropic changes (n = 6) and/or polyhydramnios (n = 5), and underwent prenatal intervention including thoracentesis, thoracoamniotic shunt placement, amnioreduction, and/or betamethasone administration. Overall survival after EXIT for lung mass resection was 89%. The average time on placental bypass was 65 minutes. Postnatal complications included reoperation for air leak (n = 1), reoperation for bleeding (n = 1), and death from sepsis and prematurity (n = 1). Venoarterial extracorporeal membrane oxygenation was used in 4 neonates for persistent pulmonary hypertension. Maternal prenatal complications included polyhydramnios (n = 5), preterm labor (n = 4), and chorioamnionitis (n = 1). One mother required perioperative blood transfusion. CONCLUSION: The EXIT procedure allows for controlled resection of large fetal lung lesions at delivery, avoiding acute respiratory decompensation related to mediastinal shift, air trapping, and compression of normal lung.
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