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Abstract Activity-dependent synaptic plasticity is known to be important in learning and memory, persistent pain and drug addiction. Glutamate NMDA receptor activation stimulates several protein kinases, which then trigger biochemical cascades that lead to modifications in synaptic efficacy. Genetic and pharmacological techniques have been used to show a role for Ca2+/calmodulin-dependent kinase II (CaMKII) in synaptic plasticity and memory formation. However, it is not known if increasing CaMKII activity in forebrain areas affects behavioral responses to tissue injury. Using genetic and pharmacological techniques, we were able to temporally and spatially restrict the over expression of CaMKII in forebrain areas. Here we show that genetic overexpression of CaMKII in the mouse forebrain selectively inhibits tissue injury-induced behavioral sensitization, including allodynia and hyperalgesia, while behavioral responses to acute noxious stimuli remain intact. CaMKII overexpression also inhibited synaptic depression induced by a prolonged repetitive stimulation in the ACC, suggesting an important role for CaMKII in the regulation of cingulate neurons. Our results suggest that neuronal CaMKII activity in the forebrain plays a role in persistent pain.

Objective: Termination of pregnancy in the 2 nd /3 rd trimester for fetal or maternal complications (i.e., for medical reasons) is an essential health service. We aimed to describe the systems-level pathways for this care in Canada., Methods: We conducted one-on-one semi-structured interviews with maternal fetal medicine (MFM), medical genetics, and nursing/social work clinicians at the 10 academic MFM sites in Canada. We conducted qualitative content analysis to identify categories describing the clinical care pathway. We triangulated data from participants within sites, and then compared data across sites to describe similarities and differences in care. We used NVivo14 Software for coding., Results: We recruited 28 participants representing all sites - 10 MFM specialists, 9 medical geneticists/genetic counsellors, and 9 nurses/social workers. We identified 4 main categories describing the clinical care pathway: (1) initial visit and clinic structure, (2) offering termination, (3) provision of procedural and medication termination, and (4) post-termination care. Across sites, although clinic structure and post-termination care were similar, there were differences in offering the option of termination (e.g. variable indications qualifying for approval), and variation in details regarding the provision of procedural and medical termination (e.g. upper gestational age limits for procedural versus medical approaches)., Conclusions: Clinical care pathways for 2 nd /3 rd trimester termination for medical reasons are variable across Canadian academic MFM centres, especially regarding circumstances under which termination is offered and details regarding the provision of procedural and medical termination. These differences provide opportunities to inform efforts to optimize equitable and comprehensive services in Canada., (Copyright © 2025. Published by Elsevier Inc.)

Purpose: We aimed to determine the incidence of mental health diagnoses and associated health and social risk factors among perinatal people in three different COVID-19 phases., Methods: We conducted a population-based, retrospective cohort study using linked administrative datasets. We included persons with live, in-hospital births in Ontario, Canada from January 1 to March 31 in 2019, 2021, or 2022 (three phases relative to COVID-19 with different public health policy measures). We excluded people with prior mental health diagnoses. We used diagnostic codes to identify new onset of depression, anxiety, or adjustment disorder in the antenatal and postpartum period. We developed multivariable, modified Poisson models to examine associations between sociodemographic and clinical factors and new mental health diagnoses in each phase., Results: There were 72,242 people in our cohort. Antenatal mental health diagnoses were significantly higher in 2021 (aRR = 1.32; CI = 1.20-1.46) and 2022 (aRR = 1.22; CI = 1.11-1.35) versus 2019. Postpartum diagnoses were significantly greater in 2021 (aRR = 1.16; CI = 1.08-1.25) versus 2019. Antenatal diagnoses were associated with birth year, previous stillbirth, pre-existing hypertension, multiparity, residential instability, and ethnocultural diversity. Postpartum diagnoses were associated with birth year, maternal age, multiparity, care provider profession, assisted reproductive technology, birthing mode, pre-existing hypertension, intensive care admission, hospital readmission, residential instability, and ethnocultural diversity. Family physicians increasingly made mental health diagnoses in 2021 and 2022., Conclusion: Increased incidence of perinatal mental health diagnoses during COVID-19 suggests complex dynamics involving pandemic and health and social risk factors., Registration: This study was registered with Clinicaltrials.gov (NCT05663762) on December 21, 2022., Competing Interests: Declaration Ethics The use of ICES data is authorized under Sect. 45 of Ontario’s Personal Health Information Protection Act (PHIPA), which allows ICES to collect and analyze health care and demographic data, without consent, for health system evaluation and improvement. Therefore, ethics approval was waived by the Hamilton Integrated Research Ethics Board (HiREB) on September 22, 2022. Competing interests The authors have no competing interests to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: There is currently limited data on cross-sensitivity between immunotherapy agents. In this case study, we report a case of severe anaphylaxis to both pembrolizumab and cemiplimab., Summary: Pembrolizumab (Keytruda) and cemiplimab (Libtayo) are both approved for the treatment of metastatic cutaneous squamous cell carcinoma. Infusion reactions occur rarely with immunotherapy agents. However, if infusion reactions are severe, the treatment should be discontinued, and there is no guidance as to whether another immunotherapy agent may be used. An 87-year-old-male was diagnosed with metastatic cutaneous squamous cell carcinoma expressing a PD-L1 combined positive score of 81%-90%. He was treated with pembrolizumab and, 15 minutes after completion of the first infusion, developed swelling of the eyelids, ears, and tongue in addition to a whole-body rash without pruritus. Due to the severity of the reaction, pembrolizumab was permanently discontinued and the patient was then started on cemiplimab. The patient received a high-dose corticosteroid as premedication before the first infusion of cemiplimab and tolerated the treatment without any adverse effects. However, when the corticosteroid premedication dose was decreased before the second cycle, the patient had a severe infusion reaction to cemiplimab requiring discontinuation., Conclusion: A patient with metastatic cutaneous squamous cell carcinoma developed a severe hypersensitivity reaction to pembrolizumab and subsequently to cemiplimab, despite premedication., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Accurate identification of fetal growth restriction in fetal autopsy is critical for assessing causes of death. We examined the impact of using a chart derived from ultrasound measurements of healthy fetuses (World Health Organization fetal growth chart) versus a chart commonly used by pathologists (Archie et al.) derived from fetal autopsy-based populations in diagnosing small-for-gestational-age (SGA) birth in perinatal deaths. Study Design: We examined perinatal deaths that underwent autopsy at BC Women's Hospital, 2015-2021. Weight centiles were assigned using the ultrasound-based fetal growth chart for birthweight and autopsy-based growth chart for autopsy weight. Results: Among 352 fetuses, 30% were SGA based on the ultrasound-based fetal growth chart versus 17% using the autopsy-based growth chart ( p  < 0.001). Weight centiles were lower when using the ultrasound-based versus autopsy-based growth chart (median difference of 9 centiles [IQR 2, 20]). Conclusions: Autopsy-based growth charts may under-classify SGA status compared to ultrasound-based fetal growth charts.

Background: Evidence suggests that women who are incarcerated desire access to contraception while incarcerated, and that this need is not currently being met. Our objective in this study was to explore the perspectives and experiences of women in prisons regarding contraception and contraception access using data from focus groups with women in a provincial prison. We analyzed focus group data collected in a provincial prison in Ontario, Canada using content analysis and a constructivist epistemology., Results: We conducted three focus groups, each approximately one hour in length. Discussions revolved around (1) knowledge and decision making about contraception, (2) accessing contraception, and (3) ideas for increasing access to contraception in the prison setting. Decision making about contraception was mainly related to concerns about side effects, consistent access to care, impacts on future fertility, and autonomy around decision-making. Participants discussed a wide range of experiences with contraception. Ideas for increasing access to contraception included information sessions, inclusion of discussions about contraception as a component of admission and release planning, and time spent in prison as a crucial juncture for decision-making about contraception., Conclusions: More qualitative research is needed to better understand the needs of women in prisons related to contraception. The findings of this study suggest that programs should focus on consistency and continuity of access to care, education opportunities, and integration of discussions about contraception into official admission and release procedures., (© 2024. The Author(s).)

Background: The Society for Maternal-Fetal Medicine recommends defining fetal growth restriction as an estimated fetal weight or abdominal circumference <10th percentile of a population-based reference. However, because multiple references are available, an understanding of their ability to identify infants at increased risk due to fetal growth restriction is critical. Previous studies have focused on the ability of different population references to identify short-term outcomes, but fetal growth restriction also has longer-term consequences for child development., Objective: This study aimed to estimate the association between estimated fetal weight percentiles on the INTERGROWTH-21 st and World Health Organization fetal growth charts and kindergarten-age childhood development, and establish the charts' discriminatory ability in predicting kindergarten-age developmental challenges., Study Design: We conducted a retrospective cohort study linking obstetrical ultrasound scans conducted at BC Women's Hospital, Vancouver, Canada, with population-based standardized kindergarten test results. The cohort was limited to nonanomalous, singleton fetuses scanned at ≥28 weeks' gestation from 2000 to 2011, with follow-up until 2017. We classified estimated fetal weight into percentiles using the INTERGROWTH-21 st and World Health Organization charts. We used generalized additive modeling to link estimated fetal weight percentile with routine province-wide kindergarten readiness test results. We calculated the area under the receiver-operating characteristic curve and other measures of diagnostic accuracy with 95% confidence intervals at select percentile cut-points of the charts. We repeated analyses using the Hadlock chart to help contextualize findings. The main outcome measure was the total Early Development Instrument score (/50). Secondary outcomes were Early Development Instrument subdomain scores for language and cognitive development, and for communication skills and general knowledge, as well as designation of "developmentally vulnerable" or "special needs"., Results: Among 3418 eligible fetuses, those with lower estimated fetal weight percentiles had systematically lower Early Development Instrument scores and increased risks of developmental vulnerability. However, the clinical significance of differences was modest in magnitude (eg, total Early Development Instrument score -2.8 [95% confidence interval, -5.1 to -0.5] in children with an estimated fetal weight in 3rd-9th percentile of INTERGROWTH-21 st chart [vs reference of 31st-90th]). The charts' predictive abilities for adverse child development were limited (eg, area under the receiver-operating characteristic curve <0.53 for all 3 charts)., Conclusion: Lower estimated fetal weight percentiles on the INTERGROWTH-21 st and World Health Organization charts indicate increased risks of adverse kindergarten-age child development at the population level, but are not accurate individual-level predictors of adverse child development., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Rates of perinatal depression and anxiety increased during the COVID-19 pandemic. It remains unclear how the COVID-19 pandemic influenced risk perception and help-seeking behaviours among pregnant and postpartum individuals., Objectives: To explore pregnant and postpartum individuals' decision-making process about when and how to seek support for feelings of depression and/or anxiety during the COVID-19 pandemic., Design: A qualitative descriptive design was used., Methods: The current study is a secondary analysis of qualitative data collected for a larger mixed-methods project that recruited participants who gave birth from 1 May 2020, to 1 December 2021, in Ontario and British Columbia, Canada, using maximum variation and purposive sampling. Seventy-three semi-structured interviews were conducted over Zoom or telephone. This analysis focuses on 56 individuals who discussed their self-identified feelings of prenatal or postpartum depression and/or anxiety. Conventional (inductive) content analysis was employed with iterative stages of open coding, focused coding and cross-checking themes., Results: Most participants recognized their need to seek help for their feelings of depression and/or anxiety through discussions with a mental health professional or someone within their social circle. Nearly all participants accessed informal social support for these feelings, which sometimes entailed social contact in contravention of local COVID-19 public health policies. Many also attempted to access formal mental healthcare, encountering barriers both related and unrelated to the pandemic. Participants described the pandemic as having the dual effect of causing or exacerbating their feelings of depression and/or anxiety while also constraining their ability to access timely professional care., Conclusion: Participants struggled to address their feelings of perinatal depression and anxiety during the COVID-19 pandemic, with many describing a lack of readily available resources and limited access to professional mental healthcare. This study highlights the need for improved provision of instrumental mental health support for pregnant and postpartum populations.

Objective: Fetal growth restriction is a common obstetrical complication that affects up to 10% of pregnancies in the general population and is most commonly due to underlying placental diseases. The purpose of this guideline is to provide summary statements and recommendations to support a clinical framework for effective screening, diagnosis, and management of pregnancies that are either at risk of or affected by fetal growth restriction., Target Population: All pregnant patients with a singleton pregnancy., Benefits, Harms, and Costs: Implementation of the recommendations in this guideline should increase clinician competency to detect fetal growth restriction and provide appropriate interventions., Evidence: Published literature in English was retrieved through searches of PubMed or MEDLINE, CINAHL, and The Cochrane Library through to September 2022 using appropriate controlled vocabulary via MeSH terms (fetal growth retardation and small for gestational age) and key words (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Results were restricted to systematic reviews, randomized controlled trials/controlled clinical trials, and observational studies. Grey 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., 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 (Table A1 for definitions and Table A2 for interpretations of strong and conditional [weak] recommendations)., Intended Audience: Obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, radiologists, and other health care providers who care for pregnant patients., Tweetable Abstract: Updated guidelines on screening, diagnosis, and management of pregnancies at risk of or affected by FGR., Summary Statements: RECOMMENDATIONS: Prediction of FGR Prevention of FGR Detection of FGR Investigations in Pregnancies with Suspected Fetal Growth Restriction Management of Early-Onset Fetal Growth Restriction Management of Late-Onset FGR Postpartum management and preconception counselling., (Copyright © 2023. Published by Elsevier Inc.)

Objectif: Le retard de croissance intra-utérin est une complication obstétricale fréquente qui touche jusqu'à 10 % des grossesses dans la population générale et qui est le plus souvent due à une pathologie placentaire sous-jacente. L'objectif de la présente directive clinique est de fournir des déclarations sommaires et des recommandations pour appuyer un protocole clinique de dépistage, diagnostic et prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes., Population Cible: Toutes les patientes enceintes menant une grossesse monofœtale. BéNéFICES, RISQUES ET COûTS: La mise en application des recommandations de la présente directive devrait améliorer la compétence des cliniciens quant à la détection du retard de croissance intra-utérin et à la réalisation des interventions indiquées. DONNéES PROBANTES: La littérature publiée a été colligée par des recherches effectuées jusqu'en septembre 2022 dans les bases de données PubMed, Medline, CINAHL et Cochrane Library en utilisant un vocabulaire contrôlé au moyen de termes MeSH pertinents (fetal growth retardation and small for gestational age) et de mots-clés (fetal growth, restriction, growth retardation, IUGR, FGR, low birth weight, small for gestational age, Doppler, placenta, pathology). Seuls les résultats de revues systématiques, d'essais cliniques randomisés ou comparatifs et d'études observationnelles ont été retenus. La littérature grise a été obtenue par des recherches menées dans des sites Web d'organismes s'intéressant à l'évaluation des technologies dans le domaine de la santé et d'organismes connexes, dans des collections de directives cliniques, des registres d'essais cliniques et des sites Web de sociétés de spécialité médicale nationales et internationales. MéTHODES DE VALIDATION: Les auteurs ont évalué la qualité des données probantes et la force des recommandations en utilisant le cadre méthodologique GRADE (Grading of Recommendations Assessment, Development and Evaluation). Voir l'annexe A en ligne (tableau A1 pour les définitions et tableau A2 pour l'interprétation des recommandations fortes et conditionnelles [faibles]). PROFESSIONNELS CONCERNéS: Obstétriciens, médecins de famille, infirmières, sages-femmes, spécialistes en médecine fœto-maternelle, radiologistes et autres professionnels de la santé qui prodiguent des soins aux patientes enceintes. RéSUMé POUR TWITTER: Mise à jour de la directive sur le dépistage, le diagnostic et la prise en charge du retard de croissance intra-utérin pour les grossesses à risque ou atteintes. DÉCLARATIONS SOMMAIRES: RECOMMANDATIONS: Prédiction du retard de croissance intra-utérin Prévention du retard de croissance intra-utérin Détection du retard de croissance intra-utérin Examens en cas de retard de croissance intra-utérin soupçonné Prise en charge du retard de croissance intra-utérin précoce Prise en charge du retard de croissance intra-utérin tardif Prise en charge du post-partum et consultations préconception., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Pregnant people have a higher risk of severe COVID-19 disease. They have been disproportionately impacted by COVID-19 infection control policies, which exacerbated conditions resulting in intimate partner violence, healthcare access, and mental health distress. This project examines the impact of accumulated individual health decisions and describes how perinatal care and health outcomes changed during the COVID-19 pandemic., Objectives: Quantitative strand: Describe differences between 2019, 2021, and 2022 birth groups related to maternal vaccination, perinatal care, and mental health care. Examine the differential impacts on racialized and low-income pregnant people.Qualitative strand: Understand how pregnant people's perceptions of COVID-19 risk influenced their decision-making about vaccination, perinatal care, social support, and mental health., Methods and Analysis: This is a Canadian convergent parallel mixed-methods study. The quantitative strand uses a retrospective cohort design to assess birth group differences in rates of Tdap and COVID-19 vaccination, gestational diabetes screening, length of post-partum hospital stay, and onset of depression, anxiety, and adjustment disorder, using administrative data from ICES, formerly the Institute for Clinical Evaluative Sciences (Ontario) and PopulationData BC (PopData) (British Columbia). Differences by socioeconomic and ethnocultural status will also be examined. The qualitative strand employs qualitative description to interview people who gave birth between May 2020- December 2021 about their COVID-19 risk perception and health decision-making process. Data integration will occur during design and interpretation., Ethics and Dissemination: This study received ethical approval from McMaster University and the University of British Columbia. Findings will be disseminated via manuscripts, presentations, and patient-facing infographics., Trial Registration: Registration: Clinicaltrials.gov registration number: NCT05663762., Competing Interests: The authors have no conflicts of interest to declare., (Copyright: © 2023 Vanstone et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To update recommendations for administration of antenatal corticosteroids in the late preterm period., Target Population: Pregnant individuals at risk of preterm birth from 34 0 to 36 6 weeks gestation., Options: Administration or non-administration of a single course of antenatal corticosteroids at 34 0 to 36 6 weeks gestation., Outcomes: Neonatal morbidity (respiratory distress, hypoglycemia), long-term neurodevelopment, and other long-term outcomes (growth, cardiac/metabolic, respiratory)., Benefits, Harms, and Costs: Administration of antenatal corticosteroids from 34 0 to 36 6 weeks gestation decreases the risk of neonatal respiratory distress but increases the risk of neonatal hypoglycemia. The long-term impacts of antenatal corticosteroid administration from 34 0 to 36 6 weeks gestation are uncertain., Evidence: For evidence on the neonatal effects of antenatal corticosteroid administration at late preterm gestation, we summarized evidence from the 2020 Cochrane review of antenatal corticosteroids and combined this with evidence from published randomized trials identified by searching Ovid MEDLINE from January 1, 2020, to May 11, 2022. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on neurodevelopmental outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on neurodevelopmental outcomes using the following sources: (1) the 2020 Cochrane review; and (2) evidence obtained by searching Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases from inception to January 5, 2022. We did not apply date or language restrictions. Given the absence of direct evidence on the impact of late preterm antenatal corticosteroid administration on other long-term outcomes, we summarized evidence on the impact of antenatal corticosteroids across gestational ages on other long-term outcomes by combining findings from the 2020 Cochrane review with evidence obtained by searching Ovid MEDLINE for observational studies related to long-term cardiometabolic, respiratory, and growth effects of antenatal corticosteroids from inception to October 22, 2021. We reviewed reference lists of included studies and relevant systematic reviews for additional references. See Appendix A for search terms and summaries., 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 B (Tables B1 for definitions and B2 for interpretations of strong and conditional [weak] recommendations)., Intended Audience: Maternity care providers, including midwives, family physicians, and obstetricians., Summary Statements: RECOMMENDATIONS., (Copyright © 2022 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: It is unclear whether the benefits of administration of antenatal corticosteroids in late preterm gestation outweigh its harms. We sought to understand whether patients and physicians need increased support to decide whether to administer antenatal corticosteroids in late preterm gestation, and their informational needs and preferences for decision-making roles related to this intervention; we also wanted to know if creation of a decision-support tool would be useful., Methods: We conducted individual, semistructured interviews with pregnant people, obstetricians and pediatricians in Vancouver, Canada, in 2019. Using a qualitative framework analysis method, we coded, charted and interpreted interview transcripts into categories that formed an analytical framework., Results: We included 20 pregnant participants, 10 obstetricians and 10 pediatricians. We organized codes into the following categories: informational needs to decide whether to administer antenatal corticosteroids; preferences for decision-making roles regarding this treatment; the need for support to make this treatment decision; and the preferred format and content of a decision-support tool. Pregnant participants wanted to be involved in decision-making about antenatal corticosteroids in late preterm gestation. They wanted information on the medication, respiratory distress, hypoglycemia, parent-neonate bonding and long-term neurodevelopment. There was variation in physician counselling practices, and in how patients and physicians perceived the balance of treatment harms and benefits. Responses suggested a decision-support tool may be useful. Participants desired clear descriptions of risk magnitude and uncertainty., Interpretation: Pregnant people and physicians would likely benefit from increased support to consider the harms and benefits of antenatal corticosteroids in late preterm gestation. Creation of a decision-support tool may be useful., Competing Interests: Competing interests: Jason Burrows is a committee chair with the Society of Obstetricians and Gynaecologists of Canada; regional division head of Maternal–Fetal Medicine with Fraser Health; regional department head and program medical director of the Maternal, Infant, Child and Youth (MICY) program with Fraser Health; chair of the quality management committee of the MICY program with Fraser Health; board member with the Canadian Obstetrics and Gynecology Review Program; and member of the department executive of the University of British Columbia Department of Obstetrics and Gynecology. Amelie Boutin reports a research scholar award from Fonds de recherche du Québec – Santé. No other competing interests were declared., (© 2023 CMA Impact Inc. or its licensors.)

Background: The external validity of randomised trials can be compromised when trial participants differ from real-world populations. In the Antenatal Late Preterm Steroids (ALPS) trial of antenatal corticosteroids at late preterm ages, participants had systematically younger gestational ages than those outside the trial setting. As risk of respiratory morbidity (the primary trial outcome) is higher at younger gestations, absolute benefits of corticosteroids calculated in the trial population may overestimate real-world treatment benefits., Objectives: To estimate the real-world absolute risk reduction and number-needed-to-treat (NNT) for antenatal corticosteroids at late preterm ages, accounting for gestational age differences between the ALPS and real-world populations., Methods: Individual participant data from the ALPS trial (which recruited 2831 women with imminent preterm birth at 34+0 to 36+5 weeks') was appended to population-based data for 15,741 women admitted for delivery between 34+0 and 36+5 weeks' from British Columbia, Canada, 2000-2013. We used logistic regression to calculate inverse odds of sampling weights for each trial participant and re-estimated treatment effects of corticosteroids on neonatal respiratory morbidity in ALPS participants, weighted to reflect the gestational age distribution of the population-based (real-world) sample., Results: The real-world absolute risk reduction was estimated to be -2.2 (95% CI -4.6, 0.0) cases of respiratory morbidity per 100, compared with -2.8 (95% CI -5.3, -0.3) in original trial data. Corresponding NNTs were 46 in the real-world setting vs 35 in the trial. Our focus on absolute measures also highlighted that the benefits of antenatal corticosteroids may be meaningfully greater at 34 weeks vs. 36 weeks (e.g., risk reductions of -3.7 vs. -1.2 per 100 respectively)., Conclusions: The absolute risk reductions and NNTs associated with antenatal corticosteroid administration at late preterm ages estimated in our study may be more appropriate for patient counselling as they better reflect the anticipated benefits of treatment when used in a real-world situation., (© 2022 John Wiley & Sons Ltd.)

As rates with which women are incarcerated have risen around the world, research examining how incarceration affects the health of people who are pregnant, their newborns, and their family members has burgeoned. Lived experience is seldom accounted for in this research, however, highlighting a gap with relevance to advocates, policy makers, researchers, and practitioners seeking to better understand health inequities and redress human suffering. In this paper we present a qualitative meta-synthesis of 31 papers reporting qualitative studies of how people who are incarcerated in prisons and jails around the world experience pregnancy, labour and childbirth, and the postpartum period. Theoretical perspectives from the reproductive justice and prison abolition movements guided our analysis, which identified connectedness (to baby) and disconnectedness (from support) as twinned themes characterizing the lived experiences of navigating pregnancy in a carceral institution. We argue that the conditions of reproductive justice - including self-determination in pregnancy, in parenting, and in managing one's reproductive capacity - are fundamentally irreconcilable with mass incarceration. We conclude by considering the strategic opportunities for health practitioners and researchers to support the movement for prison abolition by mobilizing health-focused arguments for decarceration., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: To assess the presentation of risk information in American College of Obstetricians and Gynecologists (ACOG) obstetrical Practice Bulletins., Methods: We reviewed B- and C-graded recommendations in Practice Bulletins published from January 2017 to March 2020. We calculated the proportion of recommendations and outcomes that were presented numerically and, of these, the proportion that were presented in accordance with best practices of risk communication - in absolute formats, or as absolute changes in risk from baseline risks. We categorized outcomes as harms or benefits to compare their risk presentation., Results: In 21 obstetrical Practice Bulletins, there were 125 recommendations, with 46 (37%) describing risks numerically. Sixteen of these 46 recommendations (35%) presented an absolute change in risk from a baseline risk. For harms, 65% were presented as absolute risks and 25% as relative risks. For benefits, this was 55% and 48% respectively., Conclusion: Most recommendations do not present numeric risk information. Of those that do, most do not use absolute risk measures., Practice Implications: Obstetrical practice guidelines should present numerical risk information wherever possible to support recommendations, increasing the use of absolute risk formats and absolute changes from baseline risks to increase risk comprehension., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Antenatal corticosteroids reduce respiratory morbidity in preterm infants, but their use during late preterm gestation (34-36 weeks) is limited because their safety for longer-term child neurodevelopment is unclear. We sought to determine if fetuses with higher probability of exposure to antenatal corticosteroids had increased rates of prescriptions for attention-deficit/hyperactivity disorder (ADHD) medication in childhood, using a quasiexperimental design that better controls for confounding than existing observational studies., Methods: We identified 16 358 children whose birthing parents were admitted for delivery between 31 + 0 (31 weeks, 0 days) and 36 + 6 weeks' gestation in 2000-2013, using a perinatal data registry from British Columbia, Canada, and linked their records with population-based child ADHD medication data (2000-2018). We used a regression discontinuity design to capitalize on the fact that pregnancies presenting for delivery immediately before and immediately after the clinical cut-off for antenatal corticosteroid administration of 34 + 0 weeks' gestation have very different levels of exposure to corticosteroids, but are otherwise similar with respect to confounders., Results: Over a median follow-up period of 9 years, 892 (5.5%) children had 1 or more dispensations of ADHD medication. Children whose birthing parents were admitted for delivery just before the corticosteroid clinical cut-off of 34 + 0 weeks' gestation did not appear to be more likely to be prescribed ADHD medication than those admitted just after the cut-off (rate ratio 1.1, 95% confidence interval [CI] 0.8 to 1.6; 1.3 excess cases per 100 children, 95% CI -2.5 to 5.7)., Interpretation: We found little evidence that children with higher probability of exposure to antenatal corticosteroids have higher rates of ADHD prescriptions in childhood, supporting the safety of antenatal corticosteroids for this neurodevelopmental outcome., Competing Interests: Competing interests: Amanda Skoll is chair of the examination committee with the Royal College of Physicians and Surgeons of Canada. Myriam Srour reports grants from the Canadian Institutes of Health Research and the Montréal Children’s Foundation, outside the submitted work. No other competing interests were declared., (© 2022 CMA Impact Inc. or its licensors.)

Objective: To determine how various centile cut points on the INTERGROWTH-21st (INTERGROWTH), World Health Organization (WHO), and Hadlock fetal growth charts predict perinatal morbidity/mortality, and how this relates to choosing a fetal growth chart for clinical use., Methods: We linked antenatal ultrasound measurements for fetuses > 28 weeks' gestation from the British Columbia Women's hospital ultrasound unit with the provincial perinatal database. We estimated the risk of perinatal morbidity/mortality (decreased cord pH, neonatal seizures, hypoglycemia, and perinatal death) associated with select centiles on each fetal growth chart (the 3rd, 10th, the centile identifying 10% of the population, and the optimal cut-point by Youden's Index), and determined how well each centile predicted perinatal morbidity/mortality., Results: Among 10,366 pregnancies, the 10th centile cut-point had a sensitivity of 11% (95% CI 8, 14), 13% (95% CI 10, 16), and 12% (95% CI 10, 16), to detect fetuses with perinatal morbidity/mortality on the INTERGROWTH, WHO, and Hadlock charts, respectively. All charts performed similarly in predicting perinatal morbidity/mortality (area under the curve [AUC] =0.54 for all three charts). The statistically optimal cut-points were the 39th, 31st, and 32nd centiles on the INTERGROWTH, WHO, and Hadlock charts respectively., Conclusion: The INTERGROWTH, WHO, and Hadlock fetal growth charts performed similarly in predicting perinatal morbidity/mortality, even when evaluating multiple cut points. Deciding which cut-point and chart to use may be guided by other considerations such as impact on workflow and how the chart was derived., (© 2022. The Author(s).)

Background: Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction., Methods: We will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers Clinicaltrials.gov and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight z-scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE., Discussion: This pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction., Systematic Review Registration: PROSPERO (CRD42017069688)., (© 2021. The Author(s).)

Background: Estimation of causal effects of short interpregnancy interval on pregnancy outcomes may be confounded by time-varying factors. These confounders should be ascertained at or before delivery of the first ("index") pregnancy, but are often only measured at the subsequent pregnancy., Objectives: To quantify bias induced by adjusting for time-varying confounders ascertained at the subsequent (rather than the index) pregnancy in estimated effects of short interpregnancy interval on pregnancy outcomes., Methods: We analysed linked records for births in British Columbia, Canada, 2004-2014, to women with ≥2 singleton pregnancies (n = 121 151). We used log binomial regression to compare short (<6, 6-11, 12-17 months) to 18-23-month reference intervals for 5 outcomes: perinatal mortality (stillbirth and neonatal death); small for gestational age (SGA) birth and preterm delivery (all, early, spontaneous). We calculated per cent differences between adjusted risk ratios (aRR) from two models with maternal age, low socio-economic status, body mass index, and smoking ascertained in the index pregnancy and the subsequent pregnancy. We considered relative per cent differences <5% minimal, 5%-9% modest, and ≥10% substantial., Results: Adjustment for confounders measured at the subsequent pregnancy introduced modest bias towards the null for perinatal mortality aRRs for <6-month interpregnancy intervals [-9.7%, 95% confidence interval [CI] -15.3, -6.2). SGA aRRs were minimally biased towards the null (-1.1%, 95% CI -2.6, 0.8) for <6-month intervals. While early preterm delivery aRRs were substantially biased towards the null (-10.4%, 95% CI -14.0, -6.6) for <6-month interpregnancy intervals, bias was minimal for <6-month intervals for all preterm deliveries (-0.6%, 95% CI -2.0, 0.8) and spontaneous preterm deliveries (-1.3%, 95% CI -3.1, 0.1). For all outcomes, bias was attenuated and minimal for 6-11-month and 12-17-month interpregnancy intervals., Conclusion: These findings suggest that maternally linked pregnancy data may not be needed for appropriate confounder adjustment when studying the effects of short interpregnancy interval on pregnancy outcomes., (© 2020 John Wiley & Sons Ltd.)

Objective: To explore women's experiences and perspectives of reproductive healthcare in prison., Methods: We conducted a qualitative study using semi-structured focus groups in 2018 with women in a provincial prison in Ontario, Canada. We asked participants about their experiences and perspectives of pregnancy and contraception related to healthcare in prison. We used a combination of deductive and inductive content analysis to categorize data. A concept map was generated using a reproductive justice framework., Results: The data reflected three components of a reproductive justice framework: 1) women have limited access to healthcare in prison, 2) reproductive safety and dignity influence attitudes toward pregnancy and contraception, and 3) women in prison want better reproductive healthcare. Discrimination and stigma were commonly invoked throughout women's experiences in seeking reproductive healthcare., Conclusions: Improving reproductive healthcare for women in prison is crucial to promoting reproductive justice in this population. Efforts to increase access to comprehensive, responsive, and timely reproductive healthcare should be informed by the needs and desires of women in prison and should actively seek to reduce their experience of discrimination and stigma in this context., Competing Interests: The authors have declared that no competing interests exist. One author (LP) is currently employed by a public health unit but did not participate in this study in this capacity, and this does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: To determine etiologies and outcomes of fetal hyperechogenic kidneys (HEK)., Methods: We conducted a retrospective chart review of HEK in British Columbia (January 2013-December 2019) and literature review., Results: We identified 20 cases of HEK without other anomalies (isolated) in our provincial cohort, one was lost to follow-up. Eight had testable genetic etiologies (autosomal dominant polycystic kidney disease [ADPKD], autosomal recessive polycystic kidney disease [ARPKD], Bardet-Biedl syndrome [BBS], and HNF1B-related disorder). The remaining seven did not have an identifiable genetic etiology. Of cases without a genetic etiology with postnatal follow-up (n = 6) there were no abnormalities of blood pressure, creatinine/estimated glomerular filtration rate or urinalysis identified with follow-up from 2-71 months. We report 11 cases with extrarenal anomalies (nonisolated), with outcomes and etiologies. We identified 224 reported cases of isolated HEK in the literature. A potentially testable genetic etiology was found in 128/224 (57.1%). The neonatal death rate in those with testable etiologies was 17/128 (13.3%) compared to 2/96 (2.1%) when testable etiologies were excluded., Conclusions: Genetic etiologies (ARPKD, ADPKD, BBS, HNF1B-related disorder, Beckwith-Wiedemann syndrome, tubular dysgenesis, familial nephroblastoma, and cytogenetic abnormalities) account for approximately half of prenatally isolated HEK; once excluded there are few neonatal deaths and short-term renal outcomes may be normal. There remains a paucity of knowledge about long-term renal outcomes., (© 2020 John Wiley & Sons Ltd.)

Background: Fetal growth standards (prescriptive charts derived from low-risk pregnancies) are theoretically better tools to monitor fetal growth than conventional references. We examined how modifying chart inclusion criteria influenced the resulting curves., Methods: We summarized estimated fetal weight (EFW) distributions from a hospital's routine 32-week ultrasound in all nonanomalous singleton fetuses (reference) and in those without maternal-fetal conditions affecting fetal growth (standard). We calculated EFWs for the 3rd, 5th, 10th, and 50th percentiles, and the proportion of fetuses each chart classified as small for gestational age., Results: Of 2309 fetuses in our reference, 690 (30%) met the standard's inclusion criteria. There were no meaningful differences between the EFW distributions of the reference and standard curves (50th percentile: 1989 g reference vs. 1968 g standard; 10th percentile: 1711 g reference vs. 1710 g standard), or the proportion of small for gestational age fetuses (both 9.9%)., Conclusions: In our study, there was little practical difference between a fetal growth reference and standard for detecting small infants.

Background: Maternal death surveillance in Canada relies on hospitalization data, which lacks information on the underlying cause of death. We developed a method for identifying underlying causes of maternal death, and quantified the frequency of maternal death by cause., Methods: We used data from the Discharge Abstract Database for fiscal years 2013 to 2017 to identify women who died in Canadian hospitals (excluding Quebec) while pregnant or within 1 year of the end of pregnancy. A sequential narrative based on hospital admission(s) during and after pregnancy was constituted and reviewed to assign the underlying cause of death (based on the World Health Organization's framework). Maternal deaths (i.e., while pregnant or within 42 days after the end of pregnancy) and late maternal deaths (i.e., more than 42 days to a year after the end of pregnancy) were examined separately., Results: We identified 85 maternal deaths. Direct obstetric causes included 8 deaths (9%) related to complications of spontaneous or induced abortion; 9 (11%), to hypertensive disorders of pregnancy; 15 (18%), to obstetric hemorrhage; 11 (13%), to pregnancy-related infection; 16 (19%), to other obstetric complications; and <5 (<6%), to complications of management. There were 21 (25%) maternal deaths with indirect obstetric causes, and <5 (<6%) with undetermined causes. Of 120 late maternal deaths, 16 (13%) had direct obstetric causes, among them, 9 deaths by suicide (56%). One hundred late maternal deaths (83%) had indirect obstetric causes; and <5 (<4%) had undetermined causes., Conclusions: The majority of maternal deaths in Canada have direct obstetric causes, whereas most late maternal deaths have indirect obstetric causes. Suicide is an important direct cause of late maternal death., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are growing concerns that antenatal corticosteroid administration may harm children's neurodevelopment. We investigated the safety of antenatal corticosteroid administration practices for children's overall developmental health (skills and behaviors) at early school age., Methods and Findings: We linked population health and education databases from British Columbia (BC), Canada to identify a cohort of births admitted to hospital between 31 weeks, 0 days gestation (31+0 weeks), and 36+6 weeks, 2000 to 2013, with routine early school age child development testing. We used a regression discontinuity design to compare outcomes of infants admitted just before and just after the clinical threshold for corticosteroid administration of 34+0 weeks. We estimated the median difference in the overall Early Development Instrument (EDI) score and EDI subdomain scores, as well as risk differences (RDs) for special needs designation and developmental vulnerability (<10th percentile on 2 or more subdomains). The cohort included 5,562 births admitted between 31+0 and 36+6 weeks, with a median EDI score of 40/50. We found no evidence that antenatal corticosteroid administration practices were linked with altered child development at early school age: median EDI score difference of -0.5 [95% CI: -2.2 to 1.7] (p = 0.65), RD per 100 births for special needs designation -0.5 [-4.2 to 3.1] (p = 0.96) and for developmental vulnerability of 3.9 [95% CI:-2.2 to 10.0] (p = 0.24). A limitation of our study is that the regression discontinuity design estimates the effect of antenatal corticosteroid administration at the gestational age of the discontinuity, 34 + 0 weeks, so our results may become less generalisable as gestational age moves further away from this point., Conclusions: Our study did not find that that antenatal corticosteroid administration practices were associated with child development at early school age. Our findings may be useful for supporting clinical counseling about antenatal corticosteroids administration at late preterm gestation, when the balance of harms and benefits is less clear., Competing Interests: The authors have declared that no competing interests exist.

Importance: Women who experience imprisonment have high morbidity and an increased risk of adverse pregnancy outcomes. Antenatal care could modify pregnancy-related risks, but there is a lack of evidence regarding antenatal care in this population., Objectives: To examine antenatal care quality indicators for women who experience imprisonment and to compare these data with data for the general population., Design, Setting, and Participants: This population-based, retrospective cohort study used linked correctional and health administrative data from women released from provincial prison in Ontario, Canada, in 2010 and women in the general population with deliveries at 20 weeks' gestation or greater from January 1, 2005, to December 31, 2015. Data analysis was performed from January 1, 2017, to May 4, 2020., Exposures: Pregnancies in women with time in prison during pregnancy (prison pregnancies), pregnancies in women with time in prison but not while pregnant (prison control pregnancies), and pregnancies in women in the general population (general population pregnancies)., Main Outcomes and Measures: Antenatal care quality indicators: first-trimester visit, first-trimester ultrasonography, and 8 or more antenatal care visits., Results: A total of 626 prison pregnancies in 529 women (mean [SD] age, 26.6 [5.4] years), 2327 prison control pregnancies in 1570 women (mean [SD] age, 26.2 [5.4] years), and 1 308 879 general population pregnancies in 884 063 women (mean [SD] age, 30.3 [5.3] years) were studied. Of 626 prison pregnancies, 193 women (30.8%; 95% CI, 27.1%-34.6%) had a first-trimester visit, 272 (48.4%; 95% CI, 44.4%-52.4%) had at least 8 antenatal care visits, and 209 (34.6%; 95% CI, 31.0%-38.4%) received first-trimester ultrasonography. In 2327 prison control pregnancies, 1106 women (47.5%; 95% CI, 45.3%-49.8%) had a first-trimester visit, 1356 (59.2%; 95% CI, 56.9%-61.4%) had 8 or more antenatal care visits, and 893 (38.5%; 95% CI, 36.4%-40.6%) received first-trimester ultrasonography. Compared with 1 308 879 general population pregnancies, the odds of antenatal care were lower for the first-trimester visit (odds ratios [ORs], 0.11 [95% CI, 0.09-0.13] in prison pregnancies and 0.23 [95% CI, 0.21-0.25] in prison control pregnancies), 8 or more antenatal care visits (ORs, 0.16 [95% CI, 0.14-0.19] in prison pregnancies and 0.25 [95% CI, 0.23-0.28] in prison control pregnancies), and first-trimester ultrasonography (ORs, 0.43 [95% CI, 0.36-0.50] in prison pregnancies and 0.51 [95% CI, 0.46-0.55] in prison control pregnancies)., Conclusions and Relevance: This study found that women who experienced imprisonment were substantially less likely to receive adequate antenatal care than were women in the general population whether or not they were in prison during pregnancy. Efforts are needed to improve antenatal care for this population both in prison and in the community.

Objective: To describe the population-level risk of infant and maternal outcomes for women who experience imprisonment and compare outcomes with the general population., Methods: We conducted a retrospective cohort study. We used linked correctional and health data for women released from provincial prisons in 2010. We defined three exposure groups for Ontario singleton deliveries from 2005-2015: deliveries to women who were in prison during pregnancy but not necessarily for delivery, prison pregnancies; deliveries to women who had been in prison but not while pregnant, prison controls; and general population deliveries. We compared groups using generalized estimating equations. Primary outcomes were preterm birth, low birth weight, and small for gestational age birth weight. Secondary outcomes included NICU admission, neonatal abstinence syndrome, placental abruption, and preterm prelabour rupture of membranes., Results: In prison pregnancies (n = 544) and prison controls (n = 2156), respectively, preterm birth risk was 15.5% and 12.5%, low birth weight risk was 13.0% and 11.6%, and small for gestational age birth weight risk was 18.1% and 19.2%. Adjusted for maternal age and parity and compared with general population deliveries (N = 1 284 949), odds ratios were increased for prison pregnancies and prison controls, respectively, at 2.7 (95% CI 2.2-3.4) and 2.1 (95% CI 1.9-2.4) for preterm birth, 3.1 (95% CI 2.4-3.9) and 2.7 (95% CI 2.3-3.1) for low birth weight, and 1.6 (95% CI 1.3-2.1) and 1.8 (95% CI 1.6-2.0) for small for gestational age birth weight., Conclusion: There is an increased risk of adverse infant outcomes in women who experience imprisonment compared with the general population, whether they are in prison during pregnancy or not., (Copyright © 2019 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated that short interpregnancy interval (the interval between delivery and estimated last menstrual period of a subsequent pregnancy) is associated with small for gestational age birth. It is controversial if this association is causal, as few studies have accounted for likely confounding factors such as unintended pregnancy. We examined the association between interpregnancy interval and infant birthweight, adjusting for pregnancy intention and other socio-economic and obstetrical risk factors., Methods: We used data from the Scandinavian Successive Small-for-Gestational-Age births study (1986-1988). Birthweight was expressed as a gestational age-standardised z-score., Results: Among 1406 women, a trend towards lower birthweight z-score with short interpregnancy interval was not statistically significant (unadjusted difference in birthweight z-score of -0.25, 95% confidence interval (CI) -0.55, 0.05). After adjusting for pregnancy intention, detailed measures of socio-economic status, and other covariates, the estimated magnitude of effect between interpregnancy interval and birthweight z-score was further attenuated (adjusted difference in birthweight z-score of -0.13, 95% CI -0.46, 0.20)., Conclusions: In this cohort study with detailed information on pregnancy intention and socio-economic status, short interpregnancy interval was not associated with lower birthweight. These findings suggest that previously observed associations between short interpregnancy interval and lower birthweight may reflect confounding by socio-economic and/or other unmeasured confounders., (© 2018 The Authors. Paediatric and Perinatal Epidemiology Published by John Wiley & Sons Ltd.)

There are multiple conventions for gestational age notation, which lead to different interpretations of completed weeks. This variability is exemplified by the different gestational age ranges recommended for administration of antenatal corticosteroid prophylaxis. Antenatal corticosteroid prophylaxis is widely recommended for women at risk of preterm delivery up to 34 completed weeks gestation. According to the World Health Organization, 34 completed weeks refers to the time period from the first day of the last menstrual period (day zero) to 34 weeks and 6 days of gestation (i.e., to 34 +6 34 weeks, or 244 days gestation). However, an alternative convention interprets 34 completed weeks as the period from the first day of the last menstrual period to 33 +6 36 weeks' gestation (i.e., 237 days' gestation). These inconsistencies in gestational age notation may have led to different practice recommendations for antenatal corticosteroid prophylaxis worldwide. Agreeing on the World Health Organization notation and interpretation of completed weeks may help promote clear communication within our discipline and more precise and effective knowledge dissemination., (Copyright © 2018 Society of Obstetricians and Gynaecologists of Canada. Published by Elsevier Inc. All rights reserved.)