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Objective: To review the available prenatal aneuploidy screening options and to provide updated clinical guidelines for reproductive care providers., Target Population: All pregnant persons receiving counselling and providing informed consent for prenatal screening., Benefits, Harms, and Costs: Implementation of the recommendations in this guideline should increase clinician competency to offer counselling for prenatal screening options and provide appropriate interventions. Given the variety of available options for prenatal screening with different performance, cost, and availability across Canada, appropriate counselling is of paramount importance to offer the best individual choice to Canadian pregnant persons. Prenatal screening may cause anxiety, and the decisions about prenatal diagnostic procedures are complex given the potential risk of fetal loss., Evidence: Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to July 2023, using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, non-invasive prenatal screening) and key words (prenatal screening, prenatal genetic counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1995 to July 2023., Validation Methods: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See online Appendix A (Tables A1 for definitions and A2 for interpretations)., Intended Audience: Health care providers involved in prenatal screening, including general practitioners, obstetricians, midwives, maternal-fetal medicine specialists, geneticists, and radiologists., Social Media Abstract: Non-invasive prenatal screening is the most accurate method for detecting major aneuploidies. It is not universally available in the public health system and has some limitations., Summary Statements: RECOMMENDATIONS., (Copyright © 2024. Published by Elsevier Inc.)

Background: Multiple marker screening is offered to pregnant individuals in many jurisdictions to screen for trisomies 21 and 18. On occasion, the result is 'double-positive'-a screening result that is unexpectedly positive for both aneuploidies. Although this occurs rarely, the paucity of available evidence about the outcomes of these pregnancies hinders patient counselling. This study aimed to investigate the association of double-positive results with preterm birth and other adverse perinatal outcomes., Methods: We conducted a population-based retrospective cohort study of pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, using province-wide perinatal registry data in Ontario, Canada. Pregnancies with double-positive screening results where trisomies 21 and 18 were ruled-out were compared to pregnancies with screen negative results for both aneuploidies. We used modified Poisson regression models with robust variance estimation to examine the association of double positive results with preterm birth and secondary outcomes., Results: From 429 540 pregnancies with multiple marker screening, 863 (0.2%) had a double-positive result; trisomies 21 and 18 were ruled out in 374 pregnancies, 203 of which resulted in a live birth. Among the pregnancies in the double-positive group resulting in a live birth, the risk of preterm birth was increased compared to pregnancies with a screen negative result: adjusted risk ratio (aRR) 2.6 (95%CI 2.0-3.6), adjusted risk difference (aRD) 10.5% (95%CI 5.4-15.7). In a sensitivity analysis excluding all diagnosed chromosomal abnormalities, the risk of preterm birth remained elevated to a similar degree: aRR 2.6 (95%CI 1.9-3.7), aRD 10.0% (95%CI 4.8-15.3). The risk of other adverse perinatal outcomes was also higher, including the risk of chromosomal abnormalities other than trisomies 21 and 18: aRR 81.1 (95%CI 69.4-94.8), aRD 34.0% (95%CI 29.2-38.8). Pregnancies with double-positive results were also less likely to result in a live birth, even when excluding all diagnosed chromosomal abnormalities; and at increased risk of adverse perinatal outcomes for those resulting in a live birth., Conclusion: Although rare, double-positive multiple marker screening results are associated with an increased risk of preterm birth and other adverse perinatal outcomes, even when excluding all identified chromosomal abnormalities., (© 2024. The Author(s).)

Background: Fetal Medicine Foundation (FMF) studies suggest that preterm preeclampsia can be predicted in the first trimester by combining biophysical, biochemical, and ultrasound markers and prevented using aspirin. We aimed to evaluate the FMF preterm preeclampsia screening test in nulliparous women., Methods: We conducted a prospective multicenter cohort study of nulliparous women recruited at 11 to 14 weeks. Maternal characteristics, mean arterial blood pressure, PAPP-A (pregnancy-associated plasma protein A), PlGF (placental growth factor) in maternal blood, and uterine artery pulsatility index were collected at recruitment. The risk of preterm preeclampsia was calculated by a third party blinded to pregnancy outcomes. Receiver operating characteristic curves were used to estimate the detection rate (sensitivity) and the false-positive rate (1-specificity) for preterm (<37 weeks) and for early-onset (<34 weeks) preeclampsia according to the FMF screening test and according to the American College of Obstetricians and Gynecologists criteria., Results: We recruited 7554 participants including 7325 (97%) who remained eligible after 20 weeks of which 65 (0.9%) developed preterm preeclampsia, and 22 (0.3%) developed early-onset preeclampsia. Using the FMF algorithm (cutoff of ≥1 in 110 for preterm preeclampsia), the detection rate was 63.1% for preterm preeclampsia and 77.3% for early-onset preeclampsia at a false-positive rate of 15.8%. Using the American College of Obstetricians and Gynecologists criteria, the equivalent detection rates would have been 61.5% and 59.1%, respectively, for a false-positive rate of 34.3%., Conclusions: The first-trimester FMF preeclampsia screening test predicts two-thirds of preterm preeclampsia and three-quarters of early-onset preeclampsia in nulliparous women, with a false-positive rate of ≈16%., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02189148., Competing Interests: Disclosures None.

Low- and middle-income countries are underresourced in subspecialist care. This study describes a unique maternal-fetal medicine clinical fellowship training program at Moi University School of Medicine and Moi Teaching and Referral Hospital in Eldoret, Western Kenya. The first of its kind in Eastern Africa, it has met with success in the retention of highly qualified practitioners providing complex pregnancy care to a population that has been heretofore underserved., (© 2024 The Authors.)

Decision-making in fetal cardiology is fraught with ethical issues yet education in bioethics for trainees is limited or nonexistent. In this innovation report, we describe the development of a fetal cardiology bioethics curriculum designed to address this gap. The curriculum was developed to supplement the core curriculum for cardiology fellows and fetal cardiology subspecialty trainees. The series combines didactic and interactive teaching modalities and contains 5 key components: (1) introduction to bioethics and its role in fetal cardiology, (2) counseling and pathways for compassionate terminal care, (3) case vignette-based ethical analysis and discussion cases, (4) fetal counseling considerations for shared decision-making and recommendations, (5) facilitated communications role play. The curriculum was refined using session evaluations from end users. This report describes the innovative curriculum as a starting point for further incorporation and study of bioethical education in pediatric cardiology and fetal training programs., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Ultrasonographic measurement of fetal nuchal translucency is used in prenatal screening for trisomies 21 and 18 and other conditions. A cutoff of 3.5 mm or greater is commonly used to offer follow-up investigations, such as prenatal cell-free DNA (cfDNA) screening or cytogenetic testing. Recent studies showed a possible association with chromosomal anomalies for levels less than 3.5 mm, but extant evidence has limitations., Objective: To evaluate the association between different nuchal translucency measurements and cytogenetic outcomes on a population level., Design, Setting, and Participants: This population-based retrospective cohort study used data from the Better Outcomes Registry & Network, the perinatal registry for Ontario, Canada. All singleton pregnancies with an estimated date of delivery from September 1, 2016, to March 31, 2021, were included. Data were analyzed from March 17 to August 14, 2023., Exposures: Nuchal translucency measurements were identified through multiple-marker screening results., Main Outcomes and Measures: Chromosomal anomalies were identified through all Ontario laboratory-generated prenatal and postnatal cytogenetic tests. Cytogenetic testing results, supplemented with information from cfDNA screening and clinical examination at birth, were used to identify pregnancies without chromosomal anomalies. Multivariable modified Poisson regression with robust variance estimation and adjustment for gestational age was used to compare cytogenetic outcomes for pregnancies with varying nuchal translucency measurement categories and a reference group with nuchal translucency less than 2.0 mm., Results: Of 414 268 pregnancies included in the study (mean [SD] maternal age at estimated delivery date, 31.5 [4.7] years), 359 807 (86.9%) had a nuchal translucency less than 2.0 mm; the prevalence of chromosomal anomalies in this group was 0.5%. An increased risk of chromosomal anomalies was associated with increasing nuchal translucency measurements, with an adjusted risk ratio (ARR) of 20.33 (95% CI, 17.58-23.52) and adjusted risk difference (ARD) of 9.94% (95% CI, 8.49%-11.39%) for pregnancies with measurements of 3.0 to less than 3.5 mm. The ARR was 4.97 (95% CI, 3.45-7.17) and the ARD was 1.40% (95% CI, 0.77%-2.04%) when restricted to chromosomal anomalies beyond the commonly screened aneuploidies (excluding trisomies 21, 18, and 13 and sex chromosome aneuploidies)., Conclusions and Relevance: In this cohort study of 414 268 singleton pregnancies, those with nuchal translucency measurements less than 2.0 mm were at the lowest risk of chromosomal anomalies. Risk increased with increasing measurements, including measurements less than 3.5 mm and anomalies not routinely screened by many prenatal genetic screening programs.

Objectives: Early assessment of pregnant individuals for risk of preterm preeclampsia (PE) is possible at the 11-14 week ultrasound visit using a validated multiple marker algorithm, allowing timely use of preventative low-dose acetylsalicylic acid (LDA) in high-risk patients. With no established early screening program for preterm PE in Canada, our objectives were to assess the acceptability and operational impact of routine screening for preterm PE during the 11-14 week ultrasound visit, evaluate uptake and adherence to LDA when recommended, and assess screening performance., Methods: A prospective implementation study of preterm PE screening among pregnant patients at the ultrasound unit of a tertiary obstetric centre in Toronto, Canada., Results: A total of 1057 patients were screened, with an acceptance rate of 87.1%. First-trimester ultrasound appointment time increased by a median time of 7 minutes (Interquartile range 6-9). By 16 weeks gestation, 88.7% of high-risk patients had started LDA, with adherence of 88.7%‒94.6% from 16‒36 weeks. Satisfaction with counselling was ≥7/10 in more than 95% of patients. There were 7 cases of preterm PE (0.73%), 3 in the low-risk group (0.35%), and 4 in the high-risk group (4.1%). When accounting for LDA use, the treatment-adjusted detection rate was 78.6%., Conclusions: We demonstrate successful implementation of a validated, effective screening and prevention program for preterm PE as a first step in the implementation of a broader program adaptable for cultural, access/equity considerations, and marker availability., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Maternal serum markers used for trisomy 21 screening are associated with placenta-mediated complications. Recently, there has been a transition from the traditional first-trimester screening (FTS) that included PAPP-A (pregnancy-associated plasma protein-A) and beta-hCG (human chorionic gonadotropin), to the enhanced FTS test, which added first-trimester AFP (alpha-fetoprotein) and PlGF (placental growth factor). However, whether elevated first-trimester AFP has a similar association with placenta-mediated complications to that observed for elevated second-trimester AFP remains unclear. Our objective was to estimate the association of first-trimester AFP with placenta-mediated complications and compare it with the corresponding associations of second-trimester AFP and other first-trimester serum markers., Methods: Retrospective population-based cohort study of women who underwent trisomy 21 screening in Ontario, Canada (2013-2019). The association of first-trimester AFP with placenta-mediated complications was estimated and compared with that of the traditional serum markers. The primary outcome was a composite of stillbirth or preterm placental complications (preeclampsia, birthweight less than third centile, or placental abruption)., Results: A total of 244 990 and 96 167 women underwent FTS and enhanced FTS test screening, respectively. All markers were associated with the primary outcome, but the association for elevated first-trimester AFP (adjusted relative risk [aRR], 1.57 [95% CI, 1.37-1.81]) was weaker than that observed for low PAPP-A (aRR, 2.48 [95% CI, 2.2-2.8]), low PlGF (aRR, 2.28 [95% CI, 1.97-2.64]), and elevated second-trimester AFP (aRR, 1.97 [95% CI, 1.81-2.15]). When the models were adjusted for all 4 enhanced FTS test markers, elevated first-trimester AFP was no longer associated with the primary outcome (aRR, 0.77 [95% CI, 0.58-1.02])., Conclusions: Unlike second-trimester AFP, elevated first-trimester AFP is not an independent risk factor for placenta-mediated complications., Competing Interests: Disclosures None.

Background: Cell-free fetal DNA screening is routinely offered to pregnant individuals to screen for aneuploidies. Although cell-free DNA screening is consistently more accurate than multiple-marker screening, it sometimes fails to yield a result. These test failures and their clinical implications are poorly described in the literature. Some studies suggest that a failed cell-free DNA screening result is associated with increased likelihood of cytogenetic abnormalities., Objective: This study aimed to assess the association between a failed cell-free DNA test and common aneuploidies. The objectives were to determine: (1) the proportion of test failures on first and subsequent attempts, and (2) whether a failed cell-free DNA screen on first attempt is associated with increased likelihood of common aneuploidies (trisomies 21, 18, and 13, and sex chromosome aneuploidies)., Study Design: This was a population-based retrospective cohort study using data from Ontario's prescribed maternal and child registry, Better Outcomes Registry and Network Ontario. The study included all singleton pregnancies in Ontario with an estimated date of delivery from September 1, 2016 to March 31, 2019 that had a cell-free DNA screening record in the registry. Specific outcomes (trisomies 21, 18, and 13, and sex chromosome aneuploidies) of pregnancies with a failed cell-free DNA screen on first attempt were compared with those of pregnancies with low-risk cell-free DNA-screening results using modified Poisson regression adjusted for funding status (publicly funded vs self-paid), gestational age at screening, method of conception, and maternal age for autosomal aneuploidies., Results: Our cohort included 35,146 pregnancies that had cell-free DNA screening during the study period. The overall cell-free DNA screening failure rate was 4.8% on first attempt and 2.2% after multiple attempts. An abnormal cytogenetic result for trisomies 21, 18, and 13, or sex chromosome aneuploidies was identified in 19.4% of pregnancies with a failed cell-free DNA screening for which cytogenetic testing was performed. Pregnancies with a failed cell-free DNA screen on first attempt had a relative risk of 130.3 (95% confidence interval, 64.7-262.6) for trisomy 21, trisomy 18, or trisomy 13, and a risk difference of 5.4% (95% confidence interval, 2.6-8.3), compared with pregnancies with a low-risk result. The risk of sex chromosome aneuploidies was not significantly greater in pregnancies with a failed result compared with pregnancies with a low-risk result (relative risk, 2.7; 95% confidence interval, 0.9-7.9; relative difference, 1.2%; 95% confidence interval, -0.9 to 3.2)., Conclusion: Cell-free DNA screening test failures are relatively common. Although repeated testing improves the likelihood of an informative result, pregnancies with a failed cell-free DNA screen upon first attempt remain at increased risk for common autosomal aneuploidies, but not sex chromosome aneuploidies., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The concentrations of maternal serum markers for aneuploidy screening are influenced by maternal characteristics such as race, smoking, insulin dependent diabetes mellitus (IDDM), and in vitro fertilization (IVF). Accurate risk estimation requires adjustment of initial values for these characteristics. This study aims to update and validate adjustment factors for race, smoking, and IDDM., Methods: The study included singleton pregnancies that received multiple marker screening in Ontario, Canada between January 2012, and December 2018, and had their information collected in the Better Outcomes Registry & Network (BORN) Ontario. Serum markers assessed included first trimester pregnancy-associated plasma protein A (PAPP-A), free β and total human chorionic gonadotropin (hCG), placental growth factor (PlGF) and αlpha-fetoprotein (AFP); second trimester AFP, unconjugated estriol (uE3), total hCG and inhibin A. The Mann-Whitney U test was used to assess the differences in the median multiple of the median (MoM) of serum markers between study and reference groups. New adjustment factors were generated by dividing the median MoM of a particular race, individuals who smoke tobacco, or have IDDM by those of the reference groups., Results: The study included 624,789 pregnancies. There were statistically significant differences in serum marker concentrations among pregnant individuals who were Black, Asian, or First Nations compared to a White group, those who smoked compared to Non-smoking individuals, and those with IDDM compared to Non-IDDM group. New adjustment factors for race, smoking, and IDDM were validated by comparing median MoM of serum markers corrected using the current adjustment factors and new adjustment factors generated in this study., Conclusion: The adjustment factors generated in this study can adjust the effects of race, smoking, and IDDM on serum markers more accurately., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.)

During the rapid deployment of COVID-19 vaccines in 2021, safety concerns may have led some pregnant individuals to postpone vaccination until after giving birth. This study aimed to describe temporal patterns and factors associated with COVID-19 vaccine series initiation after recent pregnancy in Ontario, Canada. Using the provincial birth registry linked with the COVID-19 vaccine database, we identified all individuals who gave birth between January 1 and December 31, 2021, and had not yet been vaccinated by the end of pregnancy, and followed them to June 30, 2022 (follow-up ranged from 6 to 18 months). We used cumulative incidence curves to describe COVID-19 vaccine initiation after pregnancy and assessed associations with sociodemographic, pregnancy-related, and health behavioral factors using Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). Among 137,198 individuals who gave birth in 2021, 87,376 (63.7%) remained unvaccinated at the end of pregnancy; of these, 65.0% initiated COVID-19 vaccination by June 30, 2022. Lower maternal age (<25 vs. 30-34 y aHR: 0.73, 95%CI: 0.70-0.77), smoking during pregnancy (vs. nonsmoking aHR: 0.68, 95%CI: 0.65-0.72), lower neighborhood income (lowest quintile vs. highest aHR: 0.79, 95%CI: 0.76-0.83), higher material deprivation (highest quintile vs. lowest aHR: 0.74, 95%CI: 0.70-0.79), and exclusive breastfeeding (vs. other feeding aHR: 0.81, 95%CI: 0.79-0.84) were associated with lower likelihood of vaccine initiation. Among unvaccinated individuals who gave birth in 2021, COVID-19 vaccine initiation after pregnancy reached 65% by June 30, 2022, suggesting persistent issues with vaccine hesitancy and/or access to vaccination in this population.

Objective: To assess risk of adverse pregnancy, fetal, and neonatal outcomes after a third dose (first booster dose) of covid-19 vaccine during pregnancy among individuals who had completed both doses of primary covid-19 vaccine series before pregnancy., Design: Population based, retrospective cohort study., Setting: Ontario, Canada, from 20 December 2021 to 31 August 2022., Participants: Individuals were included if they were pregnant with an expected date of delivery from 20 December 2021 (start date of third dose eligibility for everyone ≥18 years) to 31 August 2022, who had completed the two doses of primary covid-19 messenger RNA vaccine series before pregnancy, and became eligible for a third dose (≥six months since dose two) before the end of pregnancy., Main Outcome Measures: Pregnancy outcomes included hypertensive disorders of pregnancy, placental abruption, caesarean delivery, chorioamnionitis, and postpartum hemorrhage. Fetal and neonatal outcomes included stillbirth, preterm birth, admission to neonatal intensive care unit for >24 h, newborn 5 min Apgar score <7, and small-for-gestational age infant (<10th percentile). We estimated hazard ratios and 95% confidence intervals for study outcomes, treating dose three as a time varying exposure and adjusting for confounding using inverse probability weighting., Results: Among 32 689 births, 18 491 (56.6%) were born to individuals who received a third covid-19 dose during pregnancy. Compared with eligible individuals who did not receive a third dose during pregnancy, no increased risks were associated with receiving a third covid-19 vaccine dose during pregnancy for placental abruption (adjusted hazard ratio 0.84 (95% confidence interval 0.70 to 1.02)), chorioamnionitis (0.67 (0.49 to 0.90)), postpartum haemorrhage (1.01 (0.89 to 1.16)), caesarean delivery (0.90 (0.87 to 0.94)), stillbirth (0.56 (0.39 to 0.81)), preterm birth (0.91 (0.84 to 0.99)), neonatal intensive care unit admission (0.96 (0.90 to 1.03)), 5 min Apgar score<7 (0.96 (0.82 to 1.14)), or small-for-gestational age infant (0.86 (0.79 to 0.93))., Conclusion: Receipt of a third covid-19 vaccine dose during pregnancy was not associated with an increased risk of adverse pregnancy, fetal, or neonatal outcomes. These findings can help to inform evidence based decision making about the risks and benefits of covid-19 booster doses during pregnancy., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; KW is Chief Scientific Officer and a Director for CANImmunize Inc. He has served as a member of safety advisory boards for Medicago and Moderna., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Population-based COVID-19 vaccine coverage estimates among pregnant individuals are limited. We assessed temporal patterns in vaccine coverage (≥1 dose before or during pregnancy) and evaluated factors associated with vaccine series initiation (receiving dose 1 during pregnancy) in Ontario, Canada., Methods: We linked the provincial birth registry with COVID-19 vaccination records from December 14, 2020 to December 31, 2021 and assessed coverage rates among all pregnant individuals by month, age, and neighborhood sociodemographic characteristics. Among individuals who gave birth since April 2021-when pregnant people were prioritized for vaccination-we assessed associations between sociodemographic, behavioral, and pregnancy-related factors with vaccine series initiation using multivariable regression to estimate adjusted risk ratios (aRR) and risk differences (aRD) with 95% confidence intervals (CI)., Results: Among 221,190 pregnant individuals, vaccine coverage increased to 71.2% by December 2021. Gaps in coverage across categories of age and sociodemographic characteristics decreased over time, but did not disappear. Lower vaccine series initiation was associated with lower age (<25 vs. 30-34 years: aRR 0.53, 95%CI 0.51-0.56), smoking (vs. non-smoking: 0.64, 0.61-0.67), no first trimester prenatal care visit (vs. visit: 0.80, 0.77-0.84), and residing in neighborhoods with the lowest income (vs. highest: 0.69, 0.67-0.71). Vaccine series initiation was marginally higher among individuals with pre-existing medical conditions (vs. no conditions: 1.07, 1.04-1.10)., Conclusions: COVID-19 vaccine coverage among pregnant individuals remained lower than in the general population, and there was lower vaccine initiation by multiple characteristics., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: K. Wilson is CEO of CANImmunize Inc, which hosts a national digital immunization record, and is a member of the independent data safety board for the Medicago COVID-19 vaccine trial; there were no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess the risk of preterm birth, small for gestational age at birth, and stillbirth after covid-19 vaccination during pregnancy., Design: Population based retrospective cohort study., Setting: Ontario, Canada, 1 May to 31 December 2021., Participants: All liveborn and stillborn infants from pregnancies conceived at least 42 weeks before the end of the study period and with gestational age ≥20 weeks or birth weight ≥500 g., Main Outcome Measures: Using Cox regression, hazard ratios and 95% confidence intervals were estimated for preterm birth before 37 weeks (overall and spontaneous preterm birth), very preterm birth (<32 weeks), small for gestational age at birth (<10th centile), and stillbirth. Vaccination against covid-19 was treated as a time varying exposure in the outcome specific risk window, and propensity score weighting was used to adjust hazard ratios for potential confounding., Results: Among 85 162 births, 43 099 (50.6%) occurred in individuals who received one dose or more of a covid-19 vaccine during pregnancy-42 979 (99.7%) received an mRNA vaccine. Vaccination during pregnancy was not associated with any increased risk of overall preterm birth (6.5% among vaccinated v 6.9% among unvaccinated; adjusted hazard ratio 1.02, 95% confidence interval 0.96 to 1.08), spontaneous preterm birth (3.7% v 4.4%; 0.96, 0.90 to 1.03), or very preterm birth (0.59% v 0.89%; 0.80, 0.67 to 0.95). No increase was found in risk of small for gestational age at birth (9.1% v 9.2%; 0.98, 0.93 to 1.03) or stillbirth (0.25% v 0.44%; 0.65, 0.51 to 0.84). Findings were similar by trimester of vaccination, mRNA vaccine product, and number of doses received during pregnancy., Conclusion: The findings suggest that vaccination against covid-19 during pregnancy is not associated with a higher risk of preterm birth, small for gestational age at birth, or stillbirth., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the Public Health Agency of Canada through the Vaccine Surveillance Reference Group and the COVID-19 Immunity Task Force; SEH and LO were partly funded by the Norwegian Research Council. KW is chief executive officer of CANImmunize, which hosts a national digital immunisation record, and is a member of the independent data safety board for the Medicago covid-19 vaccine trial. There are no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We sought to determine the cost-effectiveness of noninvasive fetal RhD blood group genotyping in nonalloimmunized and alloimmunized pregnancies in Canada., Study Design and Methods: We developed two probabilistic state-transition (Markov) microsimulation models to compare fetal genotyping followed by targeted management versus usual care (i.e., universal Rh immunoglobulin [RhIG] prophylaxis in nonalloimmunized RhD-negative pregnancies, or universal intensive monitoring in alloimmunized pregnancies). The reference case considered a healthcare payer perspective and a 10-year time horizon. Sensitivity analysis examined assumptions related to test cost, paternal screening, subsequent pregnancies, other alloantibodies (e.g., K, Rh c/C/E), societal perspective, and lifetime horizon., Results: Fetal genotyping in nonalloimmunized pregnancies (at per-sample test cost of C$247/US$311) was associated with a slightly higher probability of maternal alloimmunization (22 vs. 21 per 10,000) and a reduced number of RhIG injections (1.427 vs. 1.795) than usual care. It was more expensive (C$154/US$194, 95% Credible Interval [CrI]: C$139/US$175-C$169/US$213) and had little impact on QALYs (0.0007, 95%CrI: -0.01-0.01). These results were sensitive to the test cost (threshold achieved at C$88/US$111), and inclusion of paternal screening. Fetal genotyping in alloimmunized pregnancies (at test cost of C$328/US$413) was less expensive (-C$6280/US$7903, 95% CrI: -C$6325/US$7959 to -C$6229/US$7838) and more effective (0.19 QALYs, 95% CrI 0.17-0.20) than usual care. These cost savings remained robust in sensitivity analyses., Discussion: Noninvasive fetal RhD genotyping saves resources and represents good value for the management of alloimmunized pregnancies. If the cost of genotyping is substantially decreased, the targeted intervention can become a viable option for nonalloimmunized pregnancies., (© 2022 AABB.)

Importance: There is limited comparative epidemiological evidence on outcomes associated with COVID-19 vaccination during pregnancy; monitoring pregnancy outcomes in large populations is required., Objective: To evaluate peripartum outcomes following COVID-19 vaccination during pregnancy., Design, Setting, and Participants: Population-based retrospective cohort study in Ontario, Canada, using a birth registry linked with the provincial COVID-19 immunization database. All births between December 14, 2020, and September 30, 2021, were included., Exposures: COVID-19 vaccination during pregnancy, COVID-19 vaccination after pregnancy, and no vaccination., Main Outcomes and Measures: Postpartum hemorrhage, chorioamnionitis, cesarean delivery (overall and emergency cesarean delivery), admission to neonatal intensive care unit (NICU), and low newborn 5-minute Apgar score (<7). Linear and robust Poisson regression was used to generate adjusted risk differences (aRDs) and risk ratios (aRRs), respectively, comparing cumulative incidence of outcomes in those who received COVID-19 vaccination during pregnancy with those vaccinated after pregnancy and those with no record of COVID-19 vaccination at any point. Inverse probability of treatment weights were used to adjust for confounding., Results: Among 97 590 individuals (mean [SD] age, 31.9 [4.9] years), 22 660 (23%) received at least 1 dose of COVID-19 vaccine during pregnancy (63.6% received dose 1 in the third trimester; 99.8% received an mRNA vaccine). Comparing those vaccinated during vs after pregnancy (n = 44 815), there were no significantly increased risks of postpartum hemorrhage (incidence: 3.0% vs 3.0%; aRD, -0.28 per 100 individuals [95% CI, -0.59 to 0.03]; aRR, 0.91 [95% CI, 0.82-1.02]), chorioamnionitis (0.5% vs 0.5%; aRD, -0.04 per 100 individuals [95% CI, -0.17 to 0.09]; aRR, 0.92 [95% CI, 0.70-1.21]), cesarean delivery (30.8% vs 32.2%; aRD, -2.73 per 100 individuals [95% CI, -3.59 to -1.88]; aRR, 0.92 [95% CI, 0.89-0.95]), NICU admission (11.0% vs 13.3%; aRD, -1.89 per 100 newborns [95% CI, -2.49 to -1.30]; aRR, 0.85 [95% CI, 0.80-0.90]), or low Apgar score (1.8% vs 2.0%; aRD, -0.31 per 100 newborns [95% CI, -0.56 to -0.06]; aRR, 0.84 [95% CI, 0.73-0.97]). Findings were qualitatively similar when compared with individuals who did not receive COVID-19 vaccination at any point (n = 30 115)., Conclusions and Relevance: In this population-based cohort study in Ontario, Canada, COVID-19 vaccination during pregnancy, compared with vaccination after pregnancy and with no vaccination, was not significantly associated with increased risk of adverse peripartum outcomes. Study interpretation should consider that the vaccinations received during pregnancy were primarily mRNA vaccines administered in the second and third trimester.

Objective: Noninvasive fetal rhesus D (RhD) blood group genotyping may prevent unnecessary use of anti-D immunoglobulin (RhIG) in non-alloimmunized RhD-negative pregnancies and can guide management of alloimmunized pregnancies. We conducted a systematic review of the economic literature to determine the cost-effectiveness of this intervention over usual care., Data Sources: Systematic literature searches of bibliographic databases (Ovid MEDLINE, Embase, and Cochrane) until February 26, 2019, and auto-alerts until October 30, 2020, and of grey literature sources were performed to retrieve all English-language studies., Study Selection: We included studies done in serologically confirmed non-alloimmunized or alloimmunized RhD-negative pregnancies, comparing costs and effectiveness of the intervention versus usual care., Data Extraction and Synthesis: Two reviewers extracted data from the eligible studies and assessed their methodological quality (risk of bias) using the Quality of Health Economic Studies (QHES) and Drummond tools. We narratively synthesized findings. Our review included 8 economic studies that evaluated non-invasive fetal RhD genotyping followed by targeted RhIG prophylaxis in non-alloimmunized pregnancies. Five studies further considered a subsequent alloimmunized pregnancy. The cost-effectiveness of the intervention versus usual care (e.g., universal RhIG or prophylaxis conditional on results of paternal testing) for non-alloiummunized pregnancies was inconsistent. Two studies indicated greater benefits and lower costs for the intervention, and another 2 suggested a trade-off. In 4 studies, the intervention was less effective and costlier than alternatives. Three studies were determined to be of high quality by both tools. Two of these studies favoured the intervention, and one assessed benefits in quality-adjusted life-years. No study clearly examined the cost-effectiveness of repetitive use of fetal genotyping in multiple non-alloimmunized or alloimmunized pregnancies. The cost of genotyping was the most influential parameter., Conclusion: The cost-effectiveness of noninvasive fetal RhD genotyping for non-alloimmunized pregnancies varies between studies. Potential savings from targeted management of alloimmunized pregnancies requires further research., (Copyright © 2021 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: The emergence of cell-free fetal DNA (cfDNA) testing technology has disrupted the landscape of prenatal screening for trisomies 21 (T21) and 18 (T18). Publicly funded systems around the world are grappling with how to best integrate this more accurate but costly technology, as there is limited evidence about its incremental value in real-world conditions. The objectives of this study were to describe the population-based performance of Ontario's prenatal screening program, which incorporates publicly funded cfDNA screening for specific indications, and the effect of cfDNA testing on the screening and diagnostic choices made by pregnant people., Methods: We conducted a retrospective, descriptive cohort study using routinely collected data from Better Outcomes & Registry Network (BORN) Ontario, which captures linked population data for prenatal and neonatal health encounters across Ontario. We included all singleton pregnancies with an estimated due date between Sept. 1, 2016, and Mar. 31, 2019, that underwent publicly funded prenatal screening in Ontario, and a comparison cohort from Apr. 1, 2012, and Mar. 31, 2013. We assessed performance of the screening program for the detection of T21 or T18 by calculating sensitivity, specificity, positive predictive value and negative predictive value against diagnostic cytogenetic results or birth outcomes. We assessed the impact of the program by calculating the proportion of T21 screen-positive pregnancies undergoing subsequent cfDNA screening and invasive prenatal diagnostic testing., Results: The study cohort included 373 682 pregnancies. The prenatal screening program had an uptake of 69.9%, a screen-positive rate and sensitivity of 1.6% and 89.9% for T21, and 0.2% and 80.5% for T18, respectively. The test failure rate for cfDNA screening was 2.2%. Invasive prenatal diagnostic testing decreased from 4.4% in 2012-2013 to 2.4% over the study period; 65.2% of pregnant people who received a screen-positive result from cfDNA testing went on to have invasive prenatal diagnostic testing., Interpretation: This publicly funded screening program, incorporating cfDNA analysis for common aneuploidies, showed robust performance, a substantial reduction in invasive prenatal diagnostic testing and that pregnant people exercise autonomy in their choices about prenatal screening and diagnosis., Competing Interests: Competing interests: Nan Okun reports funding from Roche Diagnostic, outside the submitted work. No other competing interests were declared., (© 2021 CMA Joule Inc. or its licensors.)

Background: Rheumatic heart disease (RHD) in sub-Saharan Africa contributes to significant cardiac morbidity and mortality, yet prevalence estimates of RHD lesions in pregnancy are lacking., Objectives: Our first aim was to evaluate women using echocardiography to estimate the prevalence of RHD and other cardiac lesions in low-risk pregnancies. Our second aim was to assess the feasibility of screening echocardiography and its acceptability to patients., Methods: We prospectively recruited 601 pregnant women from a low-risk antenatal clinic at a tertiary care maternity centre in Western Kenya. Women completed a questionnaire about past medical history and cardiac symptoms. They underwent standardized screening echocardiography to evaluate RHD and non-RHD associated cardiac lesions. Our primary outcome was RHD-associated cardiac lesions and our secondary outcome was a composite of any clinically-relevant cardiac lesion or echocardiography finding. We also recorded duration of screening echocardiography and its acceptability among pregnant women in this sample., Results: The point prevalence of RHD-associated cardiac lesions was 5.0/1,000 (95% confidence interval: 1.0-14.5), and the point prevalence of all clinically significant lesions/findings was 21.6/1,000 (11.6-36.7). Mean screening time was seven minutes (SD 1.7, range: 4-17) for women without cardiac abnormalities and 13 minutes (SD 4.6, range: 6-23) for women with abnormal findings. Echocardiography was acceptable to women with 74.2% agreeing to participate., Conclusions: The prevalence of clinically-relevant cardiac lesions was moderately high in a low-risk population of pregnant women in Western Kenya., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2021 The Author(s).)

Objective: The cost effectiveness of noninvasive prenatal testing (NIPT) has been established for high-risk pregnancies but remains unclear for pregnancies at other risk levels. The aim was to assess the cost effectiveness of NIPT in average-risk pregnancies from the perspective of a provincial public payer in Canada., Methods: A model was developed to compare traditional prenatal screening (TPS), NIPT as a second-tier test (performed only after a positive TPS result), and NIPT as a first-tier test (performed instead of TPS) for trisomies 21, 18, and 13; sex chromosome aneuploidies; and microdeletions in a hypothetical annual population cohort of average-risk pregnancies (142 000 to 148,000) in Ontario, Canada. A probabilistic analysis was conducted with 5000 repetitions., Results: Compared with TPS, NIPT as a second-tier test detected more affected fetuses with trisomies 21, 18, and 13 (188 vs. 158), substantially reduced the number of diagnostic tests (i.e., chorionic villus sampling and amniocentesis) performed (660 vs. 3107), and reduced the cost of prenatal screening ($26.7 million vs. $27.6 million) annually. Compared with second-tier NIPT, first-tier NIPT detected an additional 80 cases of trisomies 21, 18, and 13 at an additional cost of $33 million. The incremental cost per additional affected fetus detected was $412 411. Extending first-tier NIPT to include testing for sex chromosome aneuploidies and 22q11.2 deletion would increase the total screening cost., Conclusions: NIPT as a second-tier test is cost-saving compared with TPS alone. Compared with second-tier NIPT, first-tier NIPT detects more cases of chromosomal anomalies but at a substantially higher cost., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. All rights reserved.)

Objective: Ontario offers a publicly funded modified contingent model of prenatal screening for aneuploidy in which cell-free DNA (cfDNA) screening is covered for pregnancies at higher risk of fetal aneuploidy. The objective of this study was to review utilization of provincially funded cfDNA screening and adherence to the criteria laid out in Ontario prenatal screening guidelines., Methods: This was a descriptive cohort study using data collected by Ontario's prescribed maternal and child registry. The study population included all pregnant individuals who received cfDNA screening from January 2016 to December 2017., Results: The most common criteria for provincially funded cfDNA screening were advanced maternal age ≥40 years (37.7%), positive multiple marker screen (34.1%), modifying risk factors such as ultrasound soft markers (7.1%), and previous aneuploidy (5.5%). The audit demonstrated that 2.9% of funded cfDNA screens tests did not meet funding criteria, and that 11.4% of self-paid cfDNA screens could have been publicly funded., Conclusion: Reviewing and auditing the application of criteria for funded cfDNA screening using prescribed registry data allows an opportunity to identify areas where targeted education may improve adherence to standardized screening protocols, and provides a basis for reassessment of the funding model., (© 2019 John Wiley & Sons, Ltd.)

Objective: The objectives of this study were as follows: (1) to investigate the accuracy of IVF identification on the prenatal screening record from prenatal screening laboratories; (2) to compare the screening markers in IVF and non-IVF pregnancies in the population of Ontario; and (3) to propose more appropriate IVF adjustment factors for the Ontario population., Methods: Two years of IVF treatment, data from all fertility clinics in Ontario were merged with the corresponding prenatal screening data from all five prenatal screening labs. New adjustment factors for IVF were developed for each maternal serum screening marker and nuchal translucency measurement. Means and SDs and linear regression models were reported for all prenatal screening records, as well as for records that had IVF identified through the prenatal screening requisition and records that were identified through the Canadian Assisted Reproductive Technologies Register (CARTR) Plus database., Results: Significant differences between IVF and non-IVF groups on the basis of the prenatal screening requisition information and CARTR Plus information were found among the ethnicity-adjusted mean multiple of the medians for alpha fetoprotein, first trimester pregnancy-associated plasma protein A, second trimester unconjugated estradiol, first trimester human chorionic gonadotropin, total human chorionic gonadotropin, and dimeric inhibin A., Conclusion: This study proposed alternate IVF adjustment factors that will produce more accurate screening results within the population of Ontario., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)

Background: In 2014, Ontario augmented its publicly funded multiple-marker screening program for prenatal aneuploidy by incorporating cell-free fetal DNA (cffDNA) analysis for high-risk pregnancies. We assessed trends in the use of multiple-marker screening, cffDNA screening and prenatal diagnostic testing before and after implementation of public funding., Methods: We conducted a descriptive study based on data from the Better Outcomes Registry & Network (BORN) Ontario. The study population included all pregnant women in Ontario with a singleton pregnancy and an expected date of delivery between July 1, 2012, and Mar. 31, 2016, with pregnancy data captured in BORN. Pregnancy losses and terminations before 20 weeks' gestation not captured in BORN were excluded. We generated descriptive statistics to show trends and regional variations in use., Results: The study sample included 534 210 singleton pregnancies. After cffDNA screening was funded for specific indications, uptake of multiple-marker screening increased slightly, from 66.5% to 68.1% ( p < 0.001). Uptake of cffDNA screening among women with a positive multiple-marker screening result increased substantially, from 3.2% to 48.8% ( p < 0.001). In contrast, the rate of prenatal diagnostic testing in this group decreased from 54.8% to 30.8% ( p < 0.001). Although women aged 40 years or older are eligible for primary cffDNA screening, only a small decrease in the use of multiple-marker screening was observed in this group. The greatest use of cffDNA screening and greatest decline in prenatal diagnostic testing were seen in women with a level of risk for trisomy 21 of 1:101-1:200 based on multiple-marker screening., Interpretation: After public funding of cffDNA screening was implemented in Ontario, there was a significant increase in cffDNA screening and a significant decrease in prenatal diagnostic testing among women with a positive multiple-marker screening result. These changing patterns show the significant impact of public policy and funding decisions on women's choices regarding prenatal testing., Competing Interests: Competing interests: None declared., (Copyright 2018, Joule Inc. or its licensors.)

The introduction of chromosomal microarray (CMA) into the prenatal setting has involved considerable deliberation due to the wide range of possible outcomes (e.g., copy number variants of uncertain clinical significance). Such issues are typically discussed in pre-test counseling for pregnant women to support informed decision-making regarding prenatal testing options. This research study aimed to assess the level of informed decision-making with respect to prenatal CMA and the factor(s) influencing decision-making to accept CMA for the selected prenatal testing procedure (i.e., chorionic villus sampling or amniocentesis). We employed a questionnaire that was adapted from a three-dimensional measure previously used to assess informed decision-making with respect to prenatal screening for Down syndrome and neural tube defects. This measure classifies an informed decision as one that is knowledgeable, value-consistent, and deliberated. Our questionnaire also included an optional open-ended question, soliciting factors that may have influenced the participants' decision to accept prenatal CMA; these responses were analyzed qualitatively. Data analysis on 106 participants indicated that 49% made an informed decision (i.e., meeting all three criteria of knowledgeable, deliberated, and value-consistent). Analysis of 59 responses to the open-ended question showed that "the more information the better" emerged as the dominant factor influencing both informed and uninformed participants' decisions to accept prenatal CMA. Despite learning about the key issues in pre-test genetic counseling, our study classified a significant portion of women as making uninformed decisions due to insufficient knowledge, lack of deliberation, value-inconsistency, or a combination of these three measures. Future efforts should focus on developing educational approaches and counseling strategies to effectively increase the rate of informed decision-making among women offered prenatal CMA.

Background: Pregnancy and early childhood represent critical periods that impact health throughout the life-course. The Ontario Birth Study (OBS) is a pregnancy cohort study designed as a platform for research on pregnancy complications, maternal and infant health, and the developmental origins of health and disease., Methods: Pregnant women <17 weeks gestational age were recruited between 2013 and 2015 from antenatal clinics at Mount Sinai Hospital, Toronto, Canada. Life style and diet questionnaires, biospecimens, and clinical data were collected throughout the pregnancy and postpartum period at the time of clinical care. The OBS was integrated into clinical care to reduce participant burden, improve efficiency, and increase research potential., Results: There were 3181 eligible women approached for recruitment and 1374 (43%) participated in the study. Among the 1374 participants, 1272 (93%) delivered a liveborn infant and were followed to 6-10 weeks postpartum. Of the 1272 women who completed the study, 98% had at least one pregnancy blood sample collected, 97% had vaginal swabs collected, 90% completed the prenatal life style questionnaires, and 78% completed the Diet History Questionnaire. Most women (88%) were ≥30 years of age, 55% had no previous children, 24% were overweight or obese pre-pregnancy and 78% of parents had postsecondary education. Most pregnancies were singleton (3% twins), 34% delivered by caesarean section, and 6% preterm (<37 weeks gestation)., Conclusions: The OBS is a contemporary cohort with detailed data including banked biospecimens for studies of pregnancy health and the gene-environment interactions that establish developmental trajectories to health, learning, and social functioning., (© 2018 John Wiley & Sons Ltd.)

Objective: To review the available prenatal screening options in light of the recent technical advances and to provide an update of previous guidelines in the field of prenatal screening., Intended Users: Health care providers involved in prenatal screening, including general practitioners, obstetricians, midwives, maternal fetal medicine specialists, geneticists, and radiologists., Target Population: All pregnant women receiving counselling and providing informed consent for prenatal screening., Evidence: Published literature was retrieved through searches of Medline, PubMed, and the Cochrane Library in and prior to March 2016 using an appropriate controlled vocabulary (prenatal diagnosis, amniocentesis, chorionic villi sampling, non-invasive prenatal screening) and key words (prenatal screening, prenatal genetic counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies written in English and published from January 1985 to May 2016. Searches were updated on a regular basis and incorporated in the guideline. 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 speciality societies., Guideline Update: Evidence will be reviewed 5 years after publication to determine whether all or part of the guideline should be updated. However, if important new evidence is published prior to the 5-year cycle, the review process may be accelerated for a more rapid update of some recommendations., (Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Objective: Prenatal screening for trisomy 21 is a standard of care. Emerging cell-free fetal DNA (cffDNA) technologies can improve screening performance, but they are expensive. This study was conducted to propose a contingent screening model that would incorporate cffDNA technology, would remain affordable, and could be applied equitably in a publically funded system., Methods: Using performance and cost parameters from published literature, four prenatal screening strategies were compared. Scenario 1 modelled integrated prenatal screening (first trimester nuchal translucency and biochemical markers from both the first and second trimesters) with no cffDNA. Scenarios 2 and 3 modelled first trimester combined screening (FTS) and "enhanced FTS" (adding serum placental growth factor and alpha fetoprotein to FTS), respectively, with contingent cffDNA following a positive result. Scenario 4 modelled cffDNA as the primary screening test., Results: Scenario 1 provides a known detection rate (DR) of 88%, with a false positive rate (FPR) of 3.3%. Scenarios 2 and 3 result in a DR of 94% and overall FPR of 0.59% and 0.33%, respectively, comparable to the DR of 96% and FPR of 0.1% with primary cffDNA (assuming the published test failure rate of 3%). The total cost, cost per woman screened, and cost per case of trisomy 21 detected were lower with scenario 3 (enhanced FTS with contingent cffDNA) compared with primary cffDNA or scenario 2 (FTS with contingent cffDNA)., Conclusion: Enhanced FTS with contingent cffDNA following a positive result provides a similar performance to that of primary cffDNA at a substantially lower cost., (Copyright © 2017 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Introduction: Placental thickness in the second trimester of pregnancy has been associated with risks of placenta-mediated complications of pregnancy. We aimed to estimate the association between first-trimester maximum placental thickness and the subsequent risk of preeclampsia and/or the delivery of small-for-gestational-age (SGA) neonate., Methods: Prospective cohort study of women recruited at 11-14 weeks gestation. Placental thickness was measured at its apparent center and reported in multiple of median (MoM) adjusted for gestational age. Participants were followed until delivery for pregnancy outcomes. Placental measurements of participants who developed preeclampsia and/or delivered SGA neonate (defined as birth weight below 10th percentile) were compared with those who did not using non-parametric statistical analyses., Results: We recruited 991 participants at a mean gestational age of 12.7 ± 0.7 weeks of gestation. SGA (n = 52) was associated with reduced 1st trimester placental thickness (median: 0.89 MoM; interquartile (IQ): 0.75-1.02 vs 0.98 MoM; IQ: 0.84-1.15; p < 0.01). Pregnancies that developed preeclampsia (n = 20) tended to have greater placental thickness (median: 1.10 MoM; IQ: 0.93-1.25 vs 0.97 MoM; IQ: 0.84-1.14; p = 0.06) with values > 1.2 MoM significantly increasing the risk for preeclampsia (relative risk: 3.6; 95%CI: 1.5-8.6, p < 0.01). Pregnancies complicated by both SGA and preeclampsia (n = 5) had similar placental thickness in the first-trimester in comparison with uncomplicated pregnancies (median: 1.03 MoM; IQ: 0.89-1.42 vs 0.98 MoM; IQ: 0.84-1.14; p = 0.33)., Conclusion: First-trimester placental thickness diverges in pregnancies at risk of preeclampsia (increased) or SGA (decreased), but remains within normal values in pregnancies at risk of both conditions, suggesting that the underlying pathologies have some opposing effects on early placental growth. The current findings should be validated in a larger cohort., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: This guideline was written to update Canadian maternity care and reproductive healthcare providers on pre- and postconceptional reproductive carrier screening for women or couples who may be at risk of being carriers for autosomal recessive (AR), autosomal dominant (AD), or X-linked (XL) conditions, with risk of transmission to the fetus. Four previous SOGC- Canadian College of Medical Geneticists (CCMG) guidelines are updated and merged into the current document., Intended Users: All maternity care (most responsible health provider [MRHP]) and paediatric providers; maternity nursing; nurse practitioner; provincial maternity care administrator; medical student; and postgraduate resident year 1-7., Target Population: Fertile, sexually active females and their fertile, sexually active male partners who are either planning a pregnancy or are pregnant (preferably in the first trimester of pregnancy, but any gestational age is acceptable)., Options: Women and their partners will be able to obtain appropriate genetic carrier screening information and possible diagnosis of AR, AD, or XL disorders (preferably pre-conception), thereby allowing an informed choice regarding genetic carrier screening and reproductive options (e.g., prenatal diagnosis, preimplantation genetic diagnosis, egg or sperm donation, or adoption)., Outcomes: Informed reproductive decisions related to genetic carrier screening and reproductive outcomes based on family history, ethnic background, past obstetrical history, known carrier status, or genetic diagnosis. SOGC REPRODUCTIVE CARRIER SCREENING SUMMARY STATEMENT (2016): Pre-conception or prenatal education and counselling for reproductive carrier screening requires a discussion about testing within the three perinatal genetic carrier screening/diagnosis time periods, which include pre-conception, prenatal, and neonatal for conditions currently being screened for and diagnosed. This new information should be added to the standard reproductive carrier screening protocols that are already being utilized by the most responsible maternity provider through the informed consent process with the patient. (III-A; GRADE low/moderate) SOGC OVERVIEW OF RECOMMENDATIONS QUALITY AND GRADE: There was a strong observational/expert opinion (quality and grade) for the genetic carrier literature with randomized controlled trial evidence being available only for the invasive testing. Both the Canadian Task Force on Preventive Health Care quality and classification and the GRADE evidence quality and grade are provided., Evidence: MEDLINE; PubMed; government neonatal screening websites; key words/common reproductive genetic carrier screened diseases/previous SOGC Guidelines/medical academic societies (Society of Maternal-Fetal Medicine [SMFM]; American College of Medical Genetics and Genomics; American College of Obstetricians and Gynecologists [ACOG]; CCMG; Royal College Obstetrics and Gynaecology [RCOG] [UK]; American Society of Human Genetics [ASHG]; International Society of Prenatal Diagnosis [ISPD])/provincial neonatal screening policies and programs; search terms (carrier screening, prenatal screening, neonatal genetic/metabolic screening, cystic fibrosis (CF), thalassemia, hemoglobinopathy, hemophilia, Fragile X syndrome (FXS), spinal muscular atrophy, Ashkenazi Jewish carrier screening, genetic carrier screening protocols, AR, AD, XL)., Search Period: 10 years (June 2005-September 2015); initial search dates June 30, 2015 and September 15, 2015; completed final search January 4, 2016. Validation of articles was completed by primary authors RD Wilson and I De Bie., Benefits, Harms, and Cost: Benefits are to provide an evidenced based reproductive genetic carrier screening update consensus based on international opinions and publications for the use of Canadian women, who are planning a pregnancy or who are pregnant and have been identified to be at risk (personal or male partner family or reproductive history) for the transmission of a clinically significant genetic condition to their offspring with associated morbidity and/or mortality. Harm may arise from having counselling and informed testing of the carrier status of the mother, their partner, or their fetus, as well as from declining to have this counselling and informed testing or from not having the opportunity for counselling and informed testing. Costs will ensue both from the provision of opportunities for counselling and testing, as well as when no such opportunities are offered or are declined and the birth of a child with a significant inherited condition and resulting morbidity/mortality occurs; these comprise not only the health care costs to the system but also the social/financial/psychological/emotional costs to the family. These recommendations are based on expert opinion and have not been subjected to a health economics assessment and local or provincial implementation will be required., Guideline Update: This guideline is an update of four previous joint SOGC-CCMG Genetic Screening Guidelines dated 2002, 2006, 2008, and 2008 developed by the SOGC Genetic Committee in collaboration with the CCMG Prenatal Diagnosis Committee (now Clinical Practice Committee). 2016 CARRIER SCREENING RECOMMENDATIONS., (Copyright © 2016 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

The chorionicity-based evaluation of the perinatal risk in twin pregnancies after assisted reproductive technology (ART) is lacking. A retrospective review was performed of all twin pregnancies monitored prenatally and delivered at our hospital between 2010 and 2014. Chorionicity was diagnosed by ultrasound examination at first trimester and confirmed by postnatal pathology. Pregnancy and perinatal outcomes were prospectively recorded. Adjusted odds ratios (aOR) with 95% confidence intervals (CI) were calculated in a logistic regression model. A total of 1153 twin pregnancies were analyzed. The occurrence of preterm premature rupture of membranes (PPROM) was 3 times as frequent in monochorionic diamniotic (MCDA) twin pregnancies after ART as in those spontaneous counterparts (aOR 3.0; 95%CI 1.1-3.2). The prevalence of intrahepatic cholestasis of pregnancies (ICP) was significantly higher in dichorionic diamniotic (DCDA) twin pregnancies following ART compared to spontaneous DCDA pregnancies (aOR 3.3; 95%CI 1.3-5.6). Perinatal outcomes did not differ between two conception methods, either in MCDA or DCDA twin pregnancies. Based on differentiation of chorionicity, ART is associated with the increased risk of PPROM in MCDA twin pregnancies and with a higher rate of ICP in DCDA twin gestations. ART does not increase adversity of perinatal outcomes in twin pregnancies.

Objective: To determine whether the diagnosis of polycystic ovary syndrome (PCOS) independently predicts increased rates of pregnancy complications relative to control subjects, after adjusting for important confounders., Design: Retrospective cohort., Setting: Not applicable., Patient(s): A review of all pregnancies after fresh IVF with or without intracytoplasmic sperm injection transfers from December 2006 to 2012 (n = 1,084) identified 394 eligible singleton births (71 women with PCOS; 323 controls without)., Intervention(s): Not applicable., Main Outcome Measure(s): Singleton births were assessed for selected adverse pregnancy and birth outcomes., Result(s): Women with PCOS demonstrated a higher risk of developing the following pregnancy complications after adjusting for differences in age, parity, body mass index, and time to conception: gestational diabetes (adjusted odds ratio [AOR] 3.15, 95% confidence interval [CI] 1.35-7.33), hypertensive disorders of pregnancy (AOR 4.25, 95% CI 1.94-9.32), preterm birth <37 weeks (AOR 2.30, 95% CI 1.07-4.97), and large for gestational age >90th percentile (AOR 2.77, 95% CI 1.21-6.35). The increased risk of preterm birth <37 weeks was eliminated after adjusting for development of hypertensive disorders of pregnancy, whereas the increased risk of large for gestational age remained significant after adjusting for gestational diabetes mellitus status. Time to conception did not differ significantly between groups, nor did rates of antepartum hemorrhage, cesarean section, or perinatal mortality., Conclusion(s): Polycystic ovary syndrome independently predicts higher risk of adverse pregnancy outcomes after adjusting for differences in maternal age, parity, body mass index, and time to conception. This new information may be of relevance in counseling and monitoring women with PCOS, although larger prospective studies may be needed to validate our findings., (Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Maternal infections with PVB19, HCV, CMV, and HIV during the antepartum period are important health problems for which the technological capacities for screening and diagnosis during the antepartum period are available. Each of these viruses requires individual consideration for inclusion in screening and for the method of screening during the antepartum period. The availability of efficacious treatments for HCV and CMV, with demonstrable benefits to the mother or fetus, is required before antepartum screening for these infections can be justified. Screening for parvovirus B19 presents a greater concern because it meets most of the features of a screening test (Wilson’s criteria) endorsed by the WHO. There is insufficient evidence to argue strongly for implementation of antepartum PVB19 screening, but the available evidence indicates a need for large studies of potential effectiveness and costs of routine PVB19 screening, either for all pregnant woman or for those at high risk of exposure to PVB19. While the technology to screen for HCV, PVB19, and CMV certainly exists, there must be careful consideration of the downstream implications of routine screening at the level of the individual patient, the general population, and other health care resources, including laboratory infrastructure, before recommending that these infections be screened for routinely in the antepartum period. A strategy for national adoption of an opt-out screening strategy for HIV should be considered.

Objective: To provide updated information on the pre- and post-conception use of oral folic acid with or without a multivitamin/micronutrient supplement for the prevention of neural tube defects and other congenital anomalies. This will help physicians, midwives, nurses, and other health care workers to assist in the education of women about the proper use and dosage of folic acid/multivitamin supplementation before and during pregnancy., Evidence: Published literature was retrieved through searches of PubMed, Medline, CINAHL, and the Cochrane Library in January 2011 using appropriate controlled vocabulary and key words (e.g., folic acid, prenatal multivitamins, folate sensitive birth defects, congenital anomaly risk reduction, pre-conception counselling). Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies published in English from 1985 and June 2014. Searches were updated on a regular basis and incorporated in the guideline to June 2014 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. Costs, risks, and benefits: The financial costs are those of daily vitamin supplementation and eating a healthy folate-enriched diet. The risks are of a reported association of dietary folic acid supplementation with fetal epigenetic modifications and with an increased likelihood of a twin pregnancy. These associations may require consideration before initiating folic acid supplementation. The benefit of folic acid oral supplementation or dietary folate intake combined with a multivitamin/micronutrient supplement is an associated decrease in neural tube defects and perhaps in other specific birth defects and obstetrical complications., Values: The quality of evidence in the document was rated using the criteria described in the Report of the Canadian Task Force on Preventative Health Care (Table 1). Summary Statement In Canada multivitamin tablets with folic acid are usually available in 3 formats: regular over-the-counter multivitamins with 0.4 to 0.6 mg folic acid, prenatal over-the-counter multivitamins with 1.0 mg folic acid, and prescription multivitamins with 5.0 mg folic acid. (III) Recommendations 1. Women should be advised to maintain a healthy folate-rich diet; however, folic acid/multivitamin supplementation is needed to achieve the red blood cell folate levels associated with maximal protection against neural tube defect. (III-A) 2. All women in the reproductive age group (12-45 years of age) who have preserved fertility (a pregnancy is possible) should be advised about the benefits of folic acid in a multivitamin supplementation during medical wellness visits (birth control renewal, Pap testing, yearly gynaecological examination) whether or not a pregnancy is contemplated. Because so many pregnancies are unplanned, this applies to all women who may become pregnant. (III-A) 3. Folic acid supplementation is unlikely to mask vitamin B12 deficiency (pernicious anemia). Investigations (examination or laboratory) are not required prior to initiating folic acid supplementation for women with a risk for primary or recurrent neural tube or other folic acid-sensitive congenital anomalies who are considering a pregnancy. It is recommended that folic acid be taken in a multivitamin including 2.6 ug/day of vitamin B12 to mitigate even theoretical concerns. (II-2A) 4. Women at HIGH RISK, for whom a folic acid dose greater than 1 mg is indicated, taking a multivitamin tablet containing folic acid, should be advised to follow the product label and not to take more than 1 daily dose of the multivitamin supplement. Additional tablets containing only folic acid should be taken to achieve the desired dose. (II-2A) 5. Women with a LOW RISK for a neural tube defect or other folic acid-sensitive congenital anomaly and a male partner with low risk require a diet of folate-rich foods and a daily oral multivitamin supplement containing 0.4 mg folic acid for at least 2 to 3 months before conception, throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues. (II-2A) 6. Women with a MODERATE RISK for a neural tube defect or other folic acid-sensitive congenital anomaly or a male partner with moderate risk require a diet of folate-rich foods and daily oral supplementation with a multivitamin containing 1.0 mg folic acid, beginning at least 3 months before conception. Women should continue this regime until 12 weeks' gestational age. (1-A) From 12 weeks' gestational age, continuing through the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (II-2A) 7. Women with an increased or HIGH RISK for a neural tube defect, a male partner with a personal history of neural tube defect, or history of a previous neural tube defect pregnancy in either partner require a diet of folate-rich foods and a daily oral supplement with 4.0 mg folic acid for at least 3 months before conception and until 12 weeks' gestational age. From 12 weeks' gestational age, continuing throughout the pregnancy, and for 4 to 6 weeks postpartum or as long as breast-feeding continues, continued daily supplementation should consist of a multivitamin with 0.4 to 1.0 mg folic acid. (I-A). The same dietary and supplementation regime should be followed if either partner has had a previous pregnancy with a neural tube defect. (II-2A).

This document has been archived because it contains outdated information. It should not be consulted for clinical use, but for historical research only. Please visit the journal website for the most recent guidelines.

Objective: We sought to determine the interventions utilized by maternal-fetal medicine specialists in the prediction and prevention of preterm labor in higher-order multiple (HOM) gestations., Study Design: Online questionnaires and email surveys were sent to all the maternal-fetal medicine specialists in Canada (n=122). Questionnaire items included interventions physicians routinely recommended for HOM gestations including: (1) bed rest; (2) cervical length measurement on transvaginal ultrasound; (3) corticosteroids use; (4) cerclage; and (5) tocolytic therapy., Results: Response rate was 66% (81/122), with 68% of respondents in practice for >10 years. Of physicians, 91% did not routinely recommend bed rest (95% confidence interval [CI], 84.7-97.2). In all, 82% (95% CI, 73.63-90.4%) recommended routine cervical length assessment with 32.3% (95% CI, 20.7-43.2) and 37.1% (95% CI, 25.3-48.6) of this group suggesting assessment at 16-18 and 19-21 weeks, respectively. Frequency of assessment varied from biweekly (53.3%; 95% CI, 40.9-65.0), to monthly (23.3%; 95% CI, 12.8-33.1), to a single measurement repeated only if abnormal (12.5%; 95% CI, 4.5-20.8). In all, 28% (95% CI, 18.2-37.8) recommended routine administration of corticosteroids for lung maturation. Timing of administration varied, with 24% initiating steroids between 24-26 weeks, 59% between 27-28 weeks, and 17% after 28 weeks. None reported routine cerclage placement. However, 71% (95% CI, 61.1-80.8) would perform cerclage based on history or ultrasound. Of respondents, 81% (95% CI, 72.4-89.5) would consider using tocolytic agents for threatened preterm labor including calcium channel blockers (94%), nonsteroidal antiinflammatory drugs (5%), and nitroglycerin transdermal patch (24%)., Conclusion: The variable practice guidelines and paucity of data for management of HOM pregnancy places the onus on individual practitioners to develop their own management schemes. This results in heterogeneous management, which is based on conflicting international guidelines, studies, expert opinion, or past experience., (Copyright © 2015. Published by Elsevier Inc.)

Objectives: To evaluate the ability of sonographers to prospectively identify intracranial translucency and posterior brain structures at 11 to 13 weeks and to evaluate measurement reproducibility of brain stem and brain stem-occipital bone diameters on stored images., Methods: After specific training for intracranial translucency visualization, 10 nonphysician sonographers prospectively identified intracranial translucency at the 11- to 13-week scan, noting whether intracranial translucency was present, absent, or uncertain. If absent/uncertain, they documented the reason as spina bifida or an inadequate image (with reasons for the inadequate image). Measurements of brain stem and brain stem-occipital bone diameters were performed on stored images. Fifty randomly selected cases were reviewed for intraobserver and interobserver variability., Results: In 313 singleton pregnancies, the posterior brain including intracranial translucency was evaluated; 293 (93.6%) had known pregnancy outcomes. None had open spina bifida, but 7 had chromosomal or congenital abnormalities. In the remaining 286 normal fetuses, intracranial translucency was seen in 275 (96%) and uncertain in 11 (4%), due to inadequate images (top 3 reasons were fetal position [n = 8], obesity [n = 5], and retroverted uterus [n = 4]). Fetal position and gestational age were significantly associated with intracranial translucency visualization (P < .05). Intraobserver and interobserver agreement rates were moderate for measurements of brain stem diameter (intraclass correlation coefficients, 0.59 and 0.57) and substantial for brain stem-occipital bone diameter (intraclass correlation coefficients, 0.76 and 0.61). Bland-Altman analysis revealed negligible intraobserver and interobserver differences in brain stem and brain stem-occipital bone diameter measurements., Conclusions: Intracranial translucency can be prospectively identified by trained sonographers in 96% of normal fetuses at 11 to 13 weeks. Measurements of brain stem and brain stem-occipital bone diameters are reproducible., (© 2014 by the American Institute of Ultrasound in Medicine.)

Heavy chain monoclonal antibodies are being considered as alternative to whole-IgG monoclonal antibodies for certain niche applications. Protein-A chromatography which is widely used for purifying IgG monoclonal antibodies is also used for purifying heavy chain monoclonal antibodies as these molecules possess fully functional Fc regions. However, the acidic conditions used to elute bound antibody may sometimes also leach protein-A, which is immunotoxic. Low pH conditions also tend to make the mAb molecules unstable and prone to aggregation. Moreover, protein-A affinity chromatography does not remove aggregates already present in the feed. Hydrophobic interaction membrane chromatography (or HIMC) has already been studied as an alternative to protein-A chromatography for purifying whole-IgG monoclonal antibodies. This paper describes the use of HIMC for capturing a humanized chimeric heavy chain monoclonal antibody (EG2-hFC). Binding and eluting conditions were suitably optimized using pure EG2-hFC. Based on this, an HIMC method was developed for capture of EG2-hFC directly from cell culture supernatant. The EG2-hFc purity obtained in this single-step process was high. The glycan profiles of protein-A and HIMC purified monoclonal antibody samples were similar, clearly demonstrating that both techniques captured similarly glycosylated population of EG2-hFc. Moreover, this technique was able to resolve aggregates from monomeric form of the EG2-hFc., (© 2014 Wiley Periodicals, Inc.)

Objective: To review the effect of assisted human reproduction (AHR) on perinatal outcomes, to identify areas requiring further research with regard to birth outcomes and AHR, and to provide guidelines to optimize obstetrical management and counselling of prospective Canadian parents., Outcomes: This document compares perinatal outcomes of different types of AHR pregnancies with each other and with those of spontaneously conceived pregnancies. Clinicians will be better informed about the adverse outcomes that have been documented in association with AHR, including obstetrical complications, adverse perinatal outcomes, multiple gestations, structural congenital abnormalities, chromosomal abnormalities, and imprinting disorders., Evidence: Published literature was retrieved through searches of MEDLINE and the Cochrane Library from January 2005 to December 2012 using appropriate controlled vocabulary and key words (assisted reproduction, assisted reproductive technology, ovulation induction, intracytoplasmic sperm injection, embryo transfer, and in vitro fertilization). Results were not restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies; studies of all designs published in English from January 2005 to December 2012 were reviewed, and additional publications were identified from the bibliographies of these articles. Searches were updated on a regular basis and incorporated in the guideline to August 2013. 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 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 1). Summary Statements 1. There is increasing evidence that infertility or subfertility is an independent risk factor for obstetrical complications and adverse perinatal outcomes, even without the addition of assisted human reproduction. (II-2) 2. The relative risk for an imprinting phenotype such as Silver-Russell syndrome, Beckwith-Wiedemann syndrome, or Angelman syndrome is increased in the assisted reproduction population, but the actual risk for one of these phenotypes to occur in an assisted pregnancy is estimated to be low, at less than 1 in 5000. The exact biological etiology for this increased imprinting risk is likely heterogeneous and requires more research. (II-2) Recommendations 1. All men with severe oligozoospermia or azoospermia (sperm count < 5 million/hpf) should be offered genetic/clinical counselling, karyotype assessment for chromosomal abnormalities, and Y-chromosome microdeletion testing prior to in vitro fertilization with intracytoplasmic sperm injection. (II-2A) 2. All men with unexplained obstructive azoospermia should be offered genetic/clinical counselling and genetic testing for cystic fibrosis prior to in vitro fertilization with intracytoplasmic sperm injection. (II-2A) 3. Multiple pregnancy is the most powerful predictive factor for adverse maternal, obstetrical, and perinatal outcomes. Couples should be thoroughly counselled about the significant risks of multiple pregnancies associated with all assisted human reproductive treatments. (II-2A) 4. The benefits and cumulative pregnancy rates of elective single embryo transfer support a policy of using this protocol in couples with good prognosis for success, and elective single embryo transfer should be strongly encouraged in this population. (II-2A) 5. To reduce the incidence of multiple pregnancy, health care policies that support public funding for assisted human reproduction, with regulations promoting best practice regarding elective single embryo transfer, should be strongly encouraged. (II-2A) 6. Among singleton pregnancies, assisted reproductive technology is associated with increased risks of preterm birth and low birth weight infants, and ovulation induction is associated with an increased risk of low birth weight infants. Until sufficient research has clarified the independent roles of infertility and treatment for infertility, couples should be counselled about the risks associated with treatment. (II-2B) There is a role for closer obstetric surveillance of women who conceive with assisted human reproduction. (III-L) 7. There is growing evidence that pregnancy outcomes are better for cryopreserved embryos fertilized in vitro than for fresh embryo transfers. This finding supports a policy of elective single embryo transfer for women with a good prognosis (with subsequent use of cryopreserved embryos as necessary), and may reassure women who are considering in vitro fertilization. (II-2A) 8. Women and couples considering assisted human reproduction and concerned about perinatal outcomes in singleton pregnancies should be advised that (1) intracytoplasmic sperm injection does not appear to confer increased adverse perinatal or maternal risk over standard in vitro fertilization, and (2) the use of donor oocytes increases successful pregnancy rates in selected women, but even when accounting for maternal age, can increase the risks of low birth weight and preeclampsia. (II-2B) 9. Any assisted reproductive technology procedure should be prefaced by a discussion of fetal outcomes and the slight increase in the risk of congenital structural abnormalities, with emphasis on known confounding factors such as infertility and body mass index. (II-2B) 10. In pregnancies achieved by artificial reproductive technology, routine anatomic ultrasound for congenital structural abnormalities is recommended between 18 and 22 weeks. (II-2A) 11. Pregnancies conceived by intracytoplasmic sperm injection may be at increased risk of chromosomal aberrations, including sex chromosome abnormalities. Diagnostic testing should be offered after appropriate counselling. (II-2A) 12. The possible increased risk for late onset cancer due to gene dysregulation for tumour suppression requires more long-term follow-up before the true risk can be determined. (III-A) 13. The clinical application of preimplantation genetic testing in fertile couples must balance the benefits of avoiding disease transmission with the medical risks and financial burden of in vitro fertilization. (III-B) 14. Preimplantation screening for aneuploidy is associated with inconsistent findings for improving pregnancy outcomes. Any discussion of preimplantation genetic screening with patients should clarify that there is no adequate information on the long-term effect of embryo single cell biopsy. (I-C).

Polynucleotides containing consecutive tracts of guanines can adopt an intramolecular G-quadruplex structure where multiple planar tetrads of hydrogen-bound guanines stack on top of each other. Remodeling of G-quadruplexes impacts numerous aspects of nucleotide biology including transcriptional and translational control. RNA helicase associated with AU-rich element (RHAU), a member of the ATP-dependent DEX(H/D) family of RNA helicases, has been established as a major cellular quadruplex resolvase. RHAU contains a core helicase domain responsible for ATP binding/hydrolysis/helicase activity and is flanked on either side by N- and C-terminal extensions. The N-terminal extension is required for quadruplex recognition, and we have previously demonstrated complex formation between this domain and a quadruplex from human telomerase RNA. Here we used an integrated approach that includes small angle x-ray scattering, nuclear magnetic resonance spectroscopy, circular dichroism, and dynamic light scattering methods to demonstrate the recognition of G-quadruplexes by the N-terminal domain of RHAU. Based on our results, we conclude that (i) quadruplex from the human telomerase RNA and its DNA analog both adopt a disc shape in solution, (ii) RHAU53-105 adopts a defined and extended conformation in solution, and (iii) the N-terminal domain mediates an interaction with a guanine tetrad face of quadruplexes. Together, these data form the foundation for understanding the recognition of quadruplexes by the N-terminal domain of RHAU.

Objective: This study aimed to assess the quantitative impact of maternal weight discrepancy on the screen result for Down syndrome when using Integrated Prenatal Screening and First Trimester Combined Screening., Methods: The study population consisted of 78,165 women undergoing prenatal screening in Ontario, Canada, and 158 pregnancies affected with Down syndrome at one Ontario center. The study assessed quantitative alterations of the multiple of the median values of first and second-trimester serum markers and the risks of Down syndrome at a set of theoretical weight discrepancies., Results: Weight discrepancies have the greatest impact on screening results when the initial risk is close to the risk cut-off. When the weight discrepancy is 5 lb or greater and the denominator of the initial risk is within 50 of the risk cut-off, the chance that a screen result will change from positive to negative or from negative to positive is 47-55% for women undertaking Integrated Prenatal Screening. This chance is 33-43% for women undertaking First Trimester Combined Screening., Conclusion: A weight discrepancy of five or more pounds has a significant impact on the risk of Down syndrome; correction of maternal weight would improve the accuracy of the screening test., (© 2013 John Wiley & Sons, Ltd.)

Unlabelled: This article reviews the use and effectiveness of emergency cerclage for women who present with a dilated cervix in the second trimester of pregnancy and seeks to identify predictors of favorable emergency cerclage outcomes. We searched PubMed and the Cochrane Library for the period January 1995 to April 2012 and used the terms "emergency cerclage," "emergency stitch," "rescue cerclage," and "rescue stitch." Thirty-four studies in which transvaginal emergency cervical cerclage was performed in women with a dilated cervix were identified and included. Predictors of poor outcome were prolapsed membranes, evidence of intra-amniotic or systemic infection, symptomatic presentation, cervical dilatation greater than 3 cm, or cerclage after 22 weeks. According to observational and limited randomized controlled trials, the cerclage group did significantly better than the bed-rest group in mean randomization-to-delivery interval, preterm delivery before 34 weeks, and compound neonatal morbidity. The current data suggest that emergency cerclage is associated with a longer latency period and, most often, with better pregnancy outcomes when compared with bed rest. Many of the predictors of adverse outcomes appear to be associated with evidence of inflammation or infection., Target Audience: Obstetricians and gynecologists, family physicians, Learning Objectives: After completing this CME activity, physicians should be better able to review the use and evaluate the effectiveness of emergency cerclage for women who present with a dilated cervix in the second trimester, to identify predictors of favorable emergency cerclage outcomes, and to compare emergency cerclage versus bed rest.

Objective: To evaluate the status of iodine nutrition among pregnant women presenting for routine antenatal care in Toronto, Canada, as determined by the median urine iodine concentration (UIC) of this population., Methods: A cross-sectional, observational study was conducted involving 142 pregnant women recruited from four low-risk antenatal outpatient clinics in Toronto, Canada. Subjects completed a questionnaire and provided a spot urine sample for the measurement of iodine concentration., Results: Mean maternal age was 33.8 ± 4.3 years. Mean gestational age was 29.3 ± 7.8 weeks. The median UIC was 221 μg/L (interquartile range, 142 to 397 μg/L). Six women (4.2%) had urine iodine levels <50 μg/L, and 36 women (25.4%) had levels between 50 and 150 μg/L., Conclusion: This cohort of primarily Caucasian, well-educated, and relatively affluent pregnant women in Toronto, Canada, are iodine sufficient, perhaps due to universal salt iodization and/or other dietary and lifestyle factors.