Hypertension: Allen VM

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).

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).

Ferguson S, Allen VM, Craig C, Allen AC, Dodds L. · Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada. · Hypertens Pregnancy. · Pubmed #19165671 No free full text.

Abstract: OBJECTIVES: To evaluate the effect of the time interval between administering antenatal steroids needed to accelerate fetal lung maturity and indicated delivery in preterm pregnancies complicated by severe hypertension, as determined by maternal and perinatal outcomes. METHODS: The Nova Scotia Atlee Perinatal Database was used to identify a population-based cohort of women with severe hypertension who delivered an infant between 1989 and 2002. Women were included if they received antenatal steroids and required delivery between 26 and 34 weeks gestation. Multivariate logistic regression analyses were conducted to evaluate the effect of time interval on maternal and perinatal mortality, maternal hemorrhagic and hypertension-associated morbidity, and perinatal respiratory, infectious, and prematurity-associated morbidity, while controlling for confounding variables. RESULTS: 172 pregnancies satisfied inclusion and exclusion criteria. Betamethasone was the most commonly used corticosteroid to accelerate fetal lung maturity (95%). Among infants delivered at 26 to 34 weeks, adjusted analyses showed a reduction in risk of depression at birth (RR, 0.54; 95% CI, 0.24 to 0.97) and need for surfactant (RR, 0.50; 95% CI, 0.25 to 0.95) when the time interval from steroid administration to delivery was >48 hours compared with <or= 48 hours. Adjusted analyses in a subgroup of women with cesarean delivery (81% of deliveries) demonstrated no differences in rates maternal or neonatal morbidity. CONCLUSIONS: The rates of most adverse maternal and neonatal outcomes in preterm pregnancies with severe hypertension delivered at 26 to 34 weeks are not affected by timing from steroid administration to delivery. These data support the decision for delivery based mainly on obstetrical indications.

Spencer CA, Allen VM, Flowerdew G, Dooley K, Dodds L. · Perinatal Epidemiology Research Unit, Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada. · Prenat Diagn. · Pubmed #18925584 No free full text.

Abstract: OBJECTIVES: To determine if low maternal serum level of pregnancy associated plasma protein A (PAPP-A) measured in early pregnancy can predict adverse pregnancy outcomes and to examine the gestational age (GA) sampling interval for these outcomes. METHODS: This was a nested case-control study from a prospective cohort of women recruited at <20 weeks of gestation in Halifax, NS. Cases (n=248) were defined as women who had a fetal loss or developed preeclampsia, severe pregnancy-induced hypertension (PIH), or small for gestational age infant (SGA). Controls (n=244) were frequency matched to cases by GA at the time of serum sampling (6 to <20 weeks GA). Participant information was obtained from questionnaires and medical chart reviews. RESULTS: Women with a low PAPP-A measure [<or=0.4 multiples of the median (MoM)] had an adjusted odds ratio of 2.1 [95% confidence interval (CI) 1.3-3.6] compared to others (>0.4 MoM). However, performance as a screening test was poor [sensitivity=38.7%; specificity=81.6%; positive likelihood ratio (LR)=2.1; negative LR=0.75]. In the adjusted model, the 10- to 14-week GA period was the only time period where low PAPP-A was significantly associated with adverse outcomes. CONCLUSIONS: Women with a low PAPP-A early in their pregnancy have twice the risk of an adverse outcome, though PAPP-A as a one-time single marker test has limited value.

Dodds L, Fell DB, Joseph KS, Allen VM, Butler B. · Perinatal Epidemiology Research Unit, Department of Obstetrics and Gynaecology, Dalhousie University, Halifax, Nova Scotia, Canada. · Obstet Gynecol. · Pubmed #16449113 No free full text.

Abstract: OBJECTIVE: To evaluate maternal and neonatal outcomes among women with hyperemesis during pregnancy. METHODS: A population-based retrospective cohort study was conducted among women with singleton deliveries between 1988 and 2002. Hyperemetic pregnancies were defined as those requiring one or more antepartum admissions for hyperemesis before 24 weeks of gestation. Severity of hyperemesis was evaluated according to the number of antenatal hospital admissions (1 or 2 versus 3 or more) and according to weight gain during pregnancy (< 7 kg [15.4 lb] versus > or = 7 kg). Maternal outcomes evaluated included weight gain during pregnancy, gestational diabetes, gestational hypertension, labor induction, and cesarean delivery. Neonatal outcomes included 5-minute Apgar score of less than 7, low birth weight, small for gestational age, preterm delivery, and perinatal death. Logistic regression was used to generate adjusted odds ratios for all outcomes, and the odds ratios were converted to relative risks. RESULTS: Of the 156,091 singleton pregnancies, 1,270 had an admission for hyperemesis. Compared to women without hyperemesis, infants born to women with hyperemesis and with low pregnancy weight gain (< 7 kg [15.4 lb]) were more likely to be low birth weight, small for gestational age (SGA), born before 37 weeks of gestation, and have a 5-minute Apgar score of less than 7. Compared with infants born to women without hyperemesis, rates of low birth weight and preterm delivery were substantially higher among infants born to women with hyperemesis and low pregnancy weight gain (4.2% versus 12.5% and 4.9% versus 13.9%, respectively). The outcomes among infants born to women with hyperemesis with pregnancy weight gain of 7 kg (15.4 lb) or more were not different from the outcomes among women without hyperemesis. CONCLUSION: The results of this study suggest that the adverse infant outcomes associated with hyperemesis are a consequence of, and mostly limited to, women with poor maternal weight gain. LEVEL OF EVIDENCE: II-2.

Joseph KS, Young DC, Dodds L, O'Connell CM, Allen VM, Chandra S, Allen AC. · Departments of Obstetrics and Gynecology and Pediatrics, Dalhousie University Faculty of Medicine, Halifax, Nova Scotia, Canada. · Obstet Gynecol. · Pubmed #14551010 No free full text.

Abstract: OBJECTIVE: To estimate the contribution of changes in maternal characteristics (namely, age, parity, prepregnancy weight, weight gain in pregnancy, smoking status) and obstetric practice (namely, labor induction, epidural anesthesia, delivery by an obstetrician, midpelvic forceps delivery) to recent increases in primary cesarean delivery rates. METHODS: We studied all deliveries in Nova Scotia, Canada, between 1988 and 2000 after excluding women who had a previous cesarean delivery (n = 127,564). Logistic regression was used to study the effect of changes in maternal characteristics and obstetric practice on primary cesarean delivery rates. The effect of changes in midpelvic forceps delivery was examined through ecologic Poisson regression. RESULTS: Primary cesarean delivery rates increased from 13.4% of deliveries in 1988 to 17.5% in 2000. This was due to increases in cesarean deliveries for dystocia (14% increase), breech (24% increase), suspected fetal distress (21% increase), hypertension (47% increase), and miscellaneous indications (73% increase). Adjustment for maternal characteristics reduced the temporal increase in primary cesarean delivery rates between 1988-1991 and 1998-2000 from 21% (95% confidence interval [CI] 16%, 25%) to 2% (95% CI -2%, 7%). Additional adjustment for obstetric practice factors further reduced period effects. Midpelvic forceps delivery was significantly and negatively associated with primary cesarean delivery (P =.001). CONCLUSION: Recent increases in primary cesarean delivery rates are a consequence of changes in maternal characteristics. Obstetric practice, which has altered due to changes in maternal characteristics and concerns related to fetal and maternal safety, has also contributed to increases in primary cesarean delivery.