Vulnerabilities and reparative strategies during pregnancy, childbirth, and the postpartum period: moving from rhetoric to action.

Maternal outcomes throughout pregnancy, childbirth, and the postnatal period are influenced by interlinked and interdependent vulnerabilities. A comprehensive understanding of how various threats and barriers affect maternal and perinatal health is critical to plan, evaluate and improve maternal health programmes. This paper builds on the introductory paper of the Series on the determinants of maternal health by assessing vulnerabilities during pregnancy, childbirth, and the postnatal period. We synthesise and present the concept of vulnerability in pregnancy and childbirth, and map vulnerability attributes and their dynamic influence on maternal outcomes in early and late pregnancy and during childbirth and the postnatal period, with a particular focus on low-income and middle-income countries (LMICs). We summarise existing literature and present the evidence on the effects of various reparative strategies to improve pregnancy and childbirth outcomes. Lastly, we discuss the implications of the identified vulnerability attributes and reparative strategies for the efforts of policymakers, healthcare professionals, and researchers working towards improving outcomes for women and birthing people in LMICs.

Aetiology and use of antibiotics in pregnancy-related infections: results of the WHO Global Maternal Sepsis Study (GLOSS), 1-week inception cohort.

BACKGROUND: Pregnancy-related infections are important contributors to maternal sepsis and mortality. We aimed to describe clinical, microbiological characteristics and use of antibiotics by source of infection and country income, among hospitalized women with suspected or confirmed pregnancy-related infections. METHODS: We used data from WHO Global Maternal Sepsis Study (GLOSS) on maternal infections in hospitalized women, in 52 low-middle- and high-income countries conducted between November 28th and December 4th, 2017, to describe the frequencies and medians of maternal demographic, obstetric, and clinical characteristics and outcomes, methods of infection diagnosis and causative pathogens, of single source pregnancy-related infection, other than breast, and initial use of therapeutic antibiotics. We included 1456 women. RESULTS: We found infections of the genital (n = 745/1456, 51.2%) and the urinary tracts (UTI) (n = 531/1456, 36.5%) to be the most frequent. UTI (n = 339/531, 63.8%) and post-caesarean skin and soft tissue infections (SSTI) (n = 99/180, 55.0%) were the sources with more culture samples taken and microbiological confirmations. Escherichia coli was the major uropathogen (n = 103/118, 87.3%) and Staphylococcus aureus (n = 21/44, 47.7%) was the commonest pathogen in SSTI. For 13.1% (n = 191) of women, antibiotics were not prescribed on the same day of infection suspicion. Cephalosporins (n = 283/531, 53.3%) were the commonest antibiotic class prescribed for UTI, while metronidazole (n = 303/925, 32.8%) was the most prescribed for all other sources. Ceftriaxone with metronidazole was the commonest combination for the genital tract (n = 98/745, 13.2%) and SSTI (n = 22/180, 12.2%). Metronidazole (n = 137/235, 58.3%) was the most prescribed antibiotic in low-income countries while cephalosporins and co-amoxiclav (n = 129/186, 69.4%) were more commonly prescribed in high-income countries. CONCLUSIONS: Differences in antibiotics used across countries could be due to availability, local guidelines, prescribing culture, cost, and access to microbiology laboratory, despite having found similar sources and pathogens as previous studies. Better dissemination of recommendations in line with antimicrobial stewardship programmes might improve antibiotic prescription.

Description of maternal and neonatal adverse events in pregnant people immunised with COVID-19 vaccines during pregnancy in the CLAP NETWORK of sentinel sites. Nested case-control analysis of the immunization-associated risk: A study protocol.

INTRODUCTION: COVID-19 is associated with higher morbimortality in pregnant people compared with non-pregnant people. At present, the benefits of maternal immunisation are considered to outweigh the risks, and therefore, vaccination is recommended during pregnancy. However, additional information is needed on the safety of the vaccines in this population. METHODS AND ANALYSIS: This a retrospective cohort nested case-control study in pregnant people who attended maternity hospitals from eight Latin American and Caribbean countries. A perinatal electronic clinical history database with neonatal and obstetric information will be used. The proportion of pregnant people immunised with COVID-19 vaccines of the following maternal and neonatal events will be described: preterm infant, small for gestational age, low birth weight, stillbirth, neonatal death, congenital malformations, maternal near miss and maternal death. Moreover, the risk of prematurity, small for gestational age and low birth weight associated with exposure to COVID-19 vaccines will be estimated. Each case will be matched with two groups of three randomly selected controls. Controls will be matched by hospital and mother's age (±3 years) with an additional matching by delivery date and conception time in the first and second control groups, respectively. The estimated required sample size for the main analysis (exposure to any vaccine) concerning 'non-use' is at least 1009 cases (3027 controls) to detect an increased probability of vaccine-associated event risk of 30% and at least 650 cases (1950 controls) to detect 30% protection. Sensitivity and secondary analyses considering country, type of vaccine, exposure windows and completeness of immunisation will be reported. ETHICS: The study protocol was reviewed by the Ethical Review Committee on Research of the Pan American Health Organization. Patient informed consent was waived due to the retrospective design and the utilisation of anonymised data (Ref. No: PAHOERC.0546.01). Results will be disseminated in open access journals.

Neglected medium-term and long-term consequences of labour and childbirth: a systematic analysis of the burden, recommended practices, and a way forward.

Over the past three decades, substantial progress has been made in reducing maternal mortality worldwide. However, the historical focus on mortality reduction has been accompanied by comparative neglect of labour and birth complications that can emerge or persist months or years postnatally. This paper addresses these overlooked conditions, arguing that their absence from the global health agenda and national action plans has led to the misconception that they are uncommon or unimportant. The historical limitation of postnatal care services to the 6 weeks after birth is also a contributing factor. We reviewed epidemiological data on medium-term and long-term complications arising from labour and childbirth beyond 6 weeks, along with high-quality clinical guidelines for their prevention, identification, and treatment. We explore the complex interplay of human evolution, maternal physiology, and inherent predispositions that contribute to these complications. We offer actionable recommendations to change the current trajectories of these neglected conditions and help achieve the targets of Sustainable Development Goal 3. This paper is the third in a Series of four papers about maternal health in the perinatal period and beyond.

Factors affecting the implementation of calcium supplementation strategies during pregnancy to prevent pre-eclampsia: a mixed-methods systematic review.

OBJECTIVES: Daily calcium supplements are recommended for pregnant women from 20 weeks' gestation to prevent pre-eclampsia in populations with low dietary calcium intake. We aimed to improve understanding of barriers and facilitators for calcium supplement intake during pregnancy to prevent pre-eclampsia. DESIGN: Mixed-method systematic review, with confidence assessed using the Grading of Recommendations, Assessment, Development and Evaluations-Confidence in the Evidence from Reviews of Qualitative research approach. DATA SOURCES: MEDLINE and EMBASE (via Ovid), CINAHL and Global Health (via EBSCO) and grey literature databases were searched up to 17 September 2022. ELIGIBILITY CRITERIA: We included primary qualitative, quantitative and mixed-methods studies reporting implementation or use of calcium supplements during pregnancy, excluding calcium fortification and non-primary studies. No restrictions were imposed on settings, language or publication date. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers extracted data and assessed risk of bias. We analysed the qualitative data using thematic synthesis, and quantitative findings were thematically mapped to qualitative findings. We then mapped the results to behavioural change frameworks to identify barriers and facilitators. RESULTS: Eighteen reports from nine studies were included in this review. Women reported barriers to consuming calcium supplements included limited knowledge about calcium supplements and pre-eclampsia, fears and experiences of side effects, varying preferences for tablets, dosing, working schedules, being away from home and taking other supplements. Receiving information regarding pre-eclampsia and safety of calcium supplement use from reliable sources, alternative dosing options, supplement reminders, early antenatal care, free supplements and support from families and communities were reported as facilitators. Healthcare providers felt that consistent messaging about benefits and risks of calcium, training, and ensuring adequate staffing and calcium supply is available would be able to help them in promoting calcium. CONCLUSION: Relevant stakeholders should consider the identified barriers and facilitators when formulating interventions and policies on calcium supplement use. These review findings can inform implementation to ensure effective and equitable provision and scale-up of calcium interventions. PROSPERO REGISTRATION NUMBER: CRD42021239143.

Calcium supplementation to prevent pre-eclampsia: protocol for an individual participant data meta-analysis, network meta-analysis and health economic evaluation.

INTRODUCTION: Low dietary calcium intake is a risk factor for pre-eclampsia, a major contributor to maternal and perinatal mortality and morbidity worldwide. Calcium supplementation can prevent pre-eclampsia in women with low dietary calcium. However, the optimal dose and timing of calcium supplementation are not known. We plan to undertake an individual participant data (IPD) meta-analysis of randomised trials to determine the effects of various calcium supplementation regimens in preventing pre-eclampsia and its complications and rank these by effectiveness. We also aim to evaluate the cost-effectiveness of calcium supplementation to prevent pre-eclampsia. METHODS AND ANALYSIS: We will identify randomised trials on calcium supplementation before and during pregnancy by searching major electronic databases including Embase, CINAHL, MEDLINE, CENTRAL, PubMed, Scopus, AMED, LILACS, POPLINE, AIM, IMSEAR, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform, without language restrictions, from inception to February 2022. Primary researchers of the identified trials will be invited to join the International Calcium in Pregnancy Collaborative Network and share their IPD. We will check each study's IPD for consistency with the original authors before standardising and harmonising the data. We will perform a series of one-stage and two-stage IPD random-effect meta-analyses to obtain the summary intervention effects on pre-eclampsia with 95% CIs and summary treatment-covariate interactions (maternal risk status, dietary intake, timing of intervention, daily dose of calcium prescribed and total intake of calcium). Heterogeneity will be summarised using tau2, I2 and 95% prediction intervals for effect in a new study. Sensitivity analysis to explore robustness of statistical and clinical assumptions will be carried out. Minor study effects (potential publication bias) will be investigated using funnel plots. A decision analytical model for use in low-income and middle-income countries will assess the cost-effectiveness of calcium supplementation to prevent pre-eclampsia. ETHICS AND DISSEMINATION: No ethical approvals are required. We will store the data in a secure repository in an anonymised format. The results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021231276.

[Barriers in access to legal abortion in the public health system in two Argentine jurisdictions: Rosario and Autonomous City of Buenos Aires, 2019-2020]. / Barreras de acceso al aborto legal en el sistema público de salud de dos jurisdicciones de Argentina: Rosario y Ciudad Autónoma de Buenos Aires, 2019-2020.

In recent decades, decisive events shaping the political and social context surrounding abortion in Argentina culminated in the passing of the Voluntary Termination of Pregnancy (IVE in Spanish) Law in December 2020. The objective of this article is to explore the main barriers to accessing legal abortions in the public health system faced by women during 2019 and 2020 in two Argentine jurisdictions, Rosario and the Autonomous City of Buenos Aires. Based on an adaptation of the "three phases of delay" framework, surveys and semi-structured interviews with 117 women were conducted. Study participants reported difficulties in accessing information about the places and people to turn to for abortions, and most stated that pregnant individuals lack information regarding their legality. Although the majority of interviewees reported positive experiences with health services, they also identified some administrative and institutional barriers.

En las últimas décadas, en la Argentina sucedieron hechos determinantes en el contexto político y social con respecto al aborto, que culminaron con la aprobación de la Ley de Interrupción Voluntaria del Embarazo (IVE) en diciembre de 2020. El objetivo de este artículo es explorar las principales barreras que enfrentaron las mujeres en el acceso al aborto legal en el sistema público de salud de dos jurisdicciones de Argentina, Rosario y Ciudad Autónoma de Buenos Aires, en los años 2019 y 2020. A partir de una adaptación del modelo de las tres demoras, se realizaron encuestas y entrevistas semiestructuradas a 117 mujeres. Las participantes reportaron dificultades para acceder a información sobre lugares y personas donde recurrir para acceder un aborto. La mayoría de las participantes respondió que las personas gestantes no cuentan con información sobre la legalidad del aborto. Si bien la mayoría reportó haber tenido una buena experiencia con los servicios de salud, también identificaron algunas barreras administrativas e institucionales.

Oral Antihypertensives for Nonsevere Pregnancy Hypertension: Systematic Review, Network Meta- and Trial Sequential Analyses.

BACKGROUND: We aimed to address which antihypertensives are superior to placebo/no therapy or another antihypertensive for controlling nonsevere pregnancy hypertension and provide future sample size estimates for definitive evidence. METHODS: Randomized trials of antihypertensives for nonsevere pregnancy hypertension were identified from online electronic databases, to February 28, 2021 (registration URL: https://www.crd.york.ac.uk/PROSPERO/; unique identifier: CRD42020188725). Our outcomes were severe hypertension, proteinuria/preeclampsia, fetal/newborn death, small-for-gestational age infants, preterm birth, and admission to neonatal care. A Bayesian random-effects model generated estimates of direct and indirect treatment comparisons. Trial sequential analysis informed future trials needed. RESULTS: Of 1246 publications identified, 72 trials were included; 61 (6923 women) were informative. All commonly prescribed antihypertensives (labetalol, other ß-blockers, methyldopa, calcium channel blockers, and mixed/multi-drug therapy) versus placebo/no therapy reduced the risk of severe hypertension by 30% to 70%. Labetalol decreased proteinuria/preeclampsia (odds ratio, 0.73 [95% credible interval, 0.54-0.99]) and fetal/newborn death (odds ratio, 0.54 [0.30-0.98]) compared with placebo/no therapy, and proteinuria/preeclampsia compared with methyldopa (odds ratio, 0.66 [0.44-0.99]) and calcium channel blockers (odds ratio, 0.63 [0.41-0.96]). No other differences were identified, but credible intervals were wide. Trial sequential analysis indicated that 2500 to 10 000 women/arm (severe hypertension or safety outcomes) to >15 000/arm (fetal/newborn death) would be required to provide definitive evidence. CONCLUSIONS: In summary, all commonly prescribed antihypertensives in pregnancy reduce the risk of severe hypertension, but labetalol may also decrease proteinuria/preeclampsia and fetal/newborn death. Evidence is lacking for many other safety outcomes. Prohibitive sample sizes are required for definitive evidence. Real-world data are needed to individualize care.

Barreras de acceso al aborto legal en el sistema público de salud de dos jurisdicciones de Argentina: Rosario y Ciudad Autónoma de Buenos Aires, 2019-2020 / Barriers in access to legal abortion in the public health system in two Argentine jurisdictions: Rosario and Autonomous City of Buenos Aires, 2019-2020

RESUMEN En las últimas décadas, en la Argentina sucedieron hechos determinantes en el contexto político y social con respecto al aborto, que culminaron con la aprobación de la Ley de Interrupción Voluntaria del Embarazo (IVE) en diciembre de 2020. El objetivo de este artículo es explorar las principales barreras que enfrentaron las mujeres en el acceso al aborto legal en el sistema público de salud de dos jurisdicciones de Argentina, Rosario y Ciudad Autónoma de Buenos Aires, en los años 2019 y 2020. A partir de una adaptación del modelo de las tres demoras, se realizaron encuestas y entrevistas semiestructuradas a 117 mujeres. Las participantes reportaron dificultades para acceder a información sobre lugares y personas donde recurrir para acceder un aborto. La mayoría de las participantes respondió que las personas gestantes no cuentan con información sobre la legalidad del aborto. Si bien la mayoría reportó haber tenido una buena experiencia con los servicios de salud, también identificaron algunas barreras administrativas e institucionales.

ABSTRACT In recent decades, decisive events shaping the political and social context surrounding abortion in Argentina culminated in the passing of the Voluntary Termination of Pregnancy (IVE in Spanish) Law in December 2020. The objective of this article is to explore the main barriers to accessing legal abortions in the public health system faced by women during 2019 and 2020 in two Argentine jurisdictions: Rosario and the Autonomous City of Buenos Aires. Based on an adaptation of the "three phases of delay" framework, surveys and semi-structured interviews with 117 women were conducted. Study participants reported difficulties in accessing information about the places and people to turn to for abortions, and most stated that pregnant individuals lack information regarding their legality. Although the majority of interviewees reported positive experiences with health services, they also identified some administrative and institutional barriers.

Reporte temático 2022. Calidad: el desafío a dos años de la ley de aborto / Thematic report 2022. Quality: The Two-Year Challenge of the Abortion Law

Este nuevo reporte del proyecto mirar aborda la calidad en la provisión de servicios de aborto. Su objetivo es contribuir a poner en agenda una dimensión crítica de la política de abor- to a la luz de los estándares internacionales y de la propia Ley 27.610.1 También este reporte tiene la intención de dar cuenta ­a través de las voces de decisores, abogadas, proveedores y activistas de distintas provincias de Argentina- de la situación actual en materia de calidad de servicios de aborto e identificar tareas pendientes a dos años de sancionada la ley.

Paracetamol/acetaminophen (single administration) for perineal pain in the early postpartum period.

BACKGROUND: Perineal pain is a common but poorly studied adverse outcome following childbirth. Pain may result from perineal trauma due to bruising, spontaneous tears, surgical incisions (episiotomies), or in association with operative vaginal births (ventouse or forceps-assisted births). This is an update of a review last published in 2013. OBJECTIVES: To determine the efficacy of a single administration of paracetamol (acetaminophen) used in the relief of acute postpartum perineal pain. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (9 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Randomised controlled trials (RCTs), including cluster-RCTs, comparing paracetamol to placebo. We excluded quasi-RCTs and cross-over trials. Data from abstracts would be included only if authors had confirmed in writing that the data to be included in the review had come from the final analysis and would not change. DATA COLLECTION AND ANALYSIS: Two review authors assessed each study for inclusion and extracted data. One review author reviewed the decisions and confirmed calculations for pain relief scores. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: This update identified no new trials so the results remain unchanged. However, by applying the GRADE assessment of the evidence, the interpretation of main results differed from previous version of this review. We identified 10 studies involving 2044 women, but all these studies involved either three or four groups, looking at differing drugs or doses. We have only included the 1301 women who were in the paracetamol versus placebo arms of the studies. Of these, five studies (482 women) assessed 500 mg to 650 mg and six studies (797 women) assessed 1000 mg of paracetamol. One study assessed 650 mg and 1000 mg compared with placebo and contributed to both comparisons. We used a random-effects meta-analysis because of the clinical variability among studies. Studies were from the 1970s to the early 1990s, and there was insufficient information to assess the risk of bias adequately, hence the findings need to be interpreted within this context. The certainty of the evidence for the two primary outcomes on which data were available was assessed as low, downgraded for overall unclear risk of bias and for heterogeneity (I² statistic 60% or greater). More women may experience pain relief with paracetamol compared with placebo (average risk ratio (RR) 2.14, 95% confidence interval (CI) 1.59 to 2.89; 10 trials, 1279 women), and fewer women may need additional pain relief with paracetamol compared with placebo (average RR 0.34, 95% CI 0.21 to 0.55; 8 trials, 1132 women). However, the certainty of the evidence was low, downgraded for unclear overall risk of bias and substantial heterogeneity. One study used the higher dose of paracetamol (1000 mg) and reported maternal drug adverse effects. There may be little or no difference in the incidence of nausea (average RR 0.18, 95% CI 0.01 to 3.66; 1 trial, 232 women; low-certainty evidence), or sleepiness (average RR 0.89, 95% CI 0.18 to 4.30; 1 trial, 232 women; low-certainty evidence). No other maternal adverse events were reported. None of the studies assessed neonatal drug adverse effects. AUTHORS' CONCLUSIONS: A single dose of paracetamol may improve perineal pain relief following vaginal birth, and may reduce the need for additional pain relief. Potential adverse effects for both women and neonates were not appropriately assessed. Any further trials should also address the gaps in evidence concerning maternal outcomes such as satisfaction with postnatal care, maternal functioning/well-being (emotional attachment, self-efficacy, competence, autonomy, confidence, self-care, coping skills) and neonatal drug adverse effects.

Abortion-related morbidity in six Latin American and Caribbean countries: findings of the WHO/HRP multi-country survey on abortion (MCS-A).

INTRODUCTION: Abortion-related complications are a significant cause of morbidity and mortality among women in many Latin American and Caribbean (LAC) countries. The objective of this study was to characterise abortion-related complication severity, describe the management of these complications and report women's experiences with abortion care in selected countries of the Americas region. METHODS: This is a cross-sectional study of 70 health facilities across six countries in the region. We collected data on women's characteristics including socio-demographics, obstetric history, clinical information, management procedures and using Audio Computer-Assisted Self-Interviewing (ACASI) survey the experience of abortion care. Descriptive bivariate analysis was performed for women's characteristics, management of complications and reported experiences of abortion care by severity of complications, organised in five hierarchical mutually exclusive categories based on indicators present at assessment. Generalised linear estimation models were used to assess the association between women's characteristics and severity of complications. RESULTS: We collected data on 7983 women with abortion-related complications. Complications were classified as mild (46.3%), moderate (49.5%), potentially life-threatening (3.1%), near-miss cases (1.1%) and deaths (0.2%). Being single, having a gestational age of ≥13 weeks and having expelled products of conception before arrival at the facility were significantly associated with experiencing severe maternal outcomes compared with mild complications.Management of abortion-related complications included both uterotonics and uterine evacuation for two-thirds of the women while one-third received uterine evacuation only. Surgical uterine evacuation was performed in 93.2% (7437/7983) of women, being vacuum aspiration the most common one (5007/7437, 67.4%).Of the 327 women who completed the ACASI survey, 16.5% reported having an induced abortion, 12.5% of the women stated that they were not given explanations regarding their care nor were able to ask questions during their examination and treatment with percentages increasing with the severity of morbidity. CONCLUSIONS: This is one of the first studies using a standardised methodology to measure severity of abortion-related complications and women's experiences with abortion care in LAC. Results aim to inform policies and programmes addressing sexual and reproductive rights and health in the region.

Availability of facility resources and services and infection-related maternal outcomes in the WHO Global Maternal Sepsis Study: a cross-sectional study.

BACKGROUND: Infections are among the leading causes of maternal mortality and morbidity. The Global Maternal Sepsis and Neonatal Initiative, launched in 2016 by WHO and partners, sought to reduce the burden of maternal infections and sepsis and was the basis upon which the Global Maternal Sepsis Study (GLOSS) was implemented in 2017. In this Article, we aimed to describe the availability of facility resources and services and to analyse their association with maternal outcomes. METHODS: GLOSS was a facility-based, prospective, 1-week inception cohort study implemented in 713 health-care facilities in 52 countries and included 2850 hospitalised pregnant or recently pregnant women with suspected or confirmed infections. All women admitted for or in hospital with suspected or confirmed infections during pregnancy, childbirth, post partum, or post abortion at any of the participating facilities between Nov 28 and Dec 4 were eligible for inclusion. In this study, we included all GLOSS participating facilities that collected facility-level data (446 of 713 facilities). We used data obtained from individual forms completed for each enrolled woman and their newborn babies by trained researchers who checked the medical records and from facility forms completed by hospital administrators for each participating facility. We described facilities according to country income level, compliance with providing core clinical interventions and services according to women's needs and reported availability, and severity of infection-related maternal outcomes. We used a logistic multilevel mixed model for assessing the association between facility characteristics and infection-related maternal outcomes. FINDINGS: We included 446 facilities from 46 countries that enrolled 2560 women. We found a high availability of most services and resources needed for obstetric care and infection prevention. We found increased odds for severe maternal outcomes among women enrolled during the post-partum or post-abortion period from facilities located in low-income countries (adjusted odds ratio 1·84 [95% CI 1·05-3·22]) and among women enrolled during pregnancy or childbirth from non-urban facilities (adjusted odds ratio 2·44 [1·02-5·85]). Despite compliance being high overall, it was low with regards to measuring respiratory rate (85 [24%] of 355 facilities) and measuring pulse oximetry (184 [57%] of 325 facilities). INTERPRETATION: While health-care facilities caring for pregnant and recently pregnant women with suspected or confirmed infections have access to a wide range of resources and interventions, worse maternal outcomes are seen among recently pregnant women located in low-income countries than among those in higher-income countries; this trend is similar for pregnant women. Compliance with cost-effective clinical practices and timely care of women with particular individual characteristics can potentially improve infection-related maternal outcomes. FUNDING: UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, WHO, Merck for Mothers, and US Agency for International Development.

Cáncer de mama y embarazo. Estudio retrospectivo y descriptivo en la ciudad de Rosario / Breast cancer and pregnancy in Argentina: A retrospective, descriptive study in the city of Rosario

Introducción: el cáncer de mama (CM) es el cáncer más frecuente diagnosticado durante el embarazo (PABC, del inglés Pregnancy Associatied Breast Cancer), con una incidencia de 1:3.000 embarazos. Objetivo: detallar las características clínicas e histopatológicas del PABC. Comparar estadios clínicos y detallar la sobrevida de las pacientes embarazadas y puérperas. Analizar el tratamiento durante el embarazo, los resultados obstétricos y neonatales. Material y método: estudio observacional, descriptivo y retrospectivo de PABC, en el período de enero de 2008 a julio de 2019 en los hospitales públicos y privados de la ciudad de Rosario. Resultados: del total 22 pacientes, 11 se encontraban embarazadas y 11 cursando el puerperio. La edad promedio fue de 37.3 años. La edad gestacional (EG) promedio al momento del diagnóstico fue de 16.8 semanas. En cuanto al subtipo histológico; el 72.72% (16 casos) ductal, 9.1% (2 casos) lobulillar, 4.54% (1 caso) medular, 4.54% (1 caso) cribiforme y 9.1% (2 casos) sin datos. El perfil inmuhohistoquímico mostró un 36.4% (8 casos) de triple negativos, 22.73% (5 casos) de Luminales A, 22.73% (5 casos) de Luminales B, 13.64% (3 casos) Her2 positivos y 4.5% (1 caso) sin dato. Los estudios clínicos al comparar las pacientes embarazadas y puérperas fueron similares. Estadios I y II: 7 pacientes en ambos grupos, estadios III: 2 pacientes en ambos grupos y estadios IV: 2 pacientes en ambos grupos. En el seguimiento medio de las pacientes (52.8 meses) se observó el fallecimiento de 5 de ellas (2 con diagnóstico de CM durante el puerperio y 3 durante el embarazo) y una recidiva locoregional de una paciente diagnosticada en el embarzo. Durante el embarazo, 2 pacientes realizaron cirugía conservadora y linfadenectomía seguida de quimioterapia, 1 paciente quimioterapia neoadyuvante seguida de cirugía conservadora y linfadenectomía, 3 pacientes quimioterapia y 1 paciente mastectomía y linfadenectomía. En 2 casos se difirió el tratamiento luego del parto. 2 pacientes realizaron la interrupción del embarazo en el primer trimestre. La quimioterapia fue administrada finalizando el primer trimestre. La radioterapia (RT) y la hormonoterapia se difirieron posparto, ninguna paciente realizó tratamiento anti Her2 durante la gestación. Los recién nacidos (RN) expuestos a quimioterapia intraútero (6 casos) nacieron vigorosos y sanos, ninguno presentó malformaciones. Se presentó un solo caso de bajo peso para la EG. El 44.4% (4 casos) de los embarazos fue finalizado a término, mientras que la finalización pretérmino representó el 55.6% (5 casos), con una EG medio de 34.4 semanas. En el 100% de los RN pretérmino la finalización del embarazo fue programada. Conclusiones: los subtipos más frecuentes fueron los tumores luminales. Se observó mayor frecuencia de tumores biológicamente más agresivos como el triple negativo comparado con la población general. No se encontraron diferencias al comparar los estadios clínicos al momento del diagnóstico de pacientes embarazadas vs puérperas. La quimioterapia administrada luego del primer trimestre es segura para el feto. Se debe evitar el parto prematuro, dado el pronóstico negativo de la prematuridad en el desarrollo cognitivo de los RN.

Introduction: breast cancer (BC) is the most common cancer diagnosed during pregnancy with an incidence of 1:3.000 pregnancies. Objetive: to detail the clinical and histopathological charactersitics of Pregnancy-associatied Breast Cancer (PABC). To compare clinical stages and to detail the survival of pregnant and postpartum patients. To analyze the treatment during pregnancy, and the obstetric and neonatal outcomes. Material and method: a retrospective, descriptive, and observational study of PABC was carried otu from january 2008 to july 2019 in the state and private hospitals of the city of Rosario. Results: of a total of 22 patients, 11 were pregnant and 11 were in the postpartum period. The patient´s average age was 37.3 years old. The average gestational age (GA) at the time of diagnosis was 16.8 weeks. As for the hitological subtype; 72.72% (16 cases) ductal, 9.1% (2 cases) lobular, 4.54% (1 case) cribriform and 9.1% (2 cases) without data. The immunohistochemical profile showed 36.4% triple negative, 22.73% of Luminal A, 22.73% of Luminal B, 13.64% HER2 positive, and 4.5% without data. The clinical stages when comparing pregnant and postpartum patients were similar. Stages I and II: 7 patients in both groups, stage III: 2 patients in both groups and stage IV: 2 patients in both groups. In the mean follow-up of the patients (52.8 moths), the death of 5 of them was detected (2 with a dignosis of BC during the puerperium and 3 during pregnancy) and a locoreginal recurrence of a patient diagnosed in pregnancy. During pregnancy, 2 patients underwent conservative surgery and lymphadenectomy followed by chemotherapy, 1 patient neoadjuvant chemotherapy followed by conservative surgery and lymphadenectomy, 3 patients chemotherapy and 1 patient underwent mastectomy and lymphadenectomy. In 2 cases, treatment was postponed after delivery. 2 patients performed the termination of pregnancy in the firts trimester. Chemotherapy was performed after the firts trimester. Radiotherapy (RT) and hormone therapy were postpartum deferred. None of the patients underwent anti-Her2 treatment during pregnancy. Newborns exposed to intrauterine chemotherapy (6 cases) were born vigorous and healthy, none of them presented malformations. Only one case presented low weight for gestational age. 44.4% of the pregnancies were due on term, while 55.6% were preterm births, with and average gestational age of 34.4% weeks. In 100% of preterm born infants, the end of the pregnancy was scheduled. Conclusions: the most frequent subtype were lumianl tumors. A preponderance of biologically more aggresive tumors such as triple negative was observed. The clinical stages at the time of diagnosis of pregnant and postpartum patients were similar. Chemotherapy after the first trimester is safe for the fetus. If possible, preterm bith should be avoided, giver the negative pronostic effect of prematurity on cognitive development.

Intravenous versus intramuscular prophylactic oxytocin for the third stage of labour.

BACKGROUND: There is general agreement that oxytocin given either through the intravenous or intramuscular route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This review was first published in 2012 and last updated in 2018. OBJECTIVES: To determine the comparative effectiveness and safety of oxytocin administered intravenously or intramuscularly for prophylactic management of the third stage of labour after vaginal birth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (19 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: Eligible studies were randomised trials comparing intravenous with intramuscular oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the certainty of the evidence with the GRADE approach. MAIN RESULTS: Seven trials, involving 7817 women, met the inclusion criteria for this review. The trials compared intravenous versus intramuscular administration of oxytocin just after the birth of the anterior shoulder or soon after the birth of the baby. All trials were conducted in hospital settings and included women with term pregnancies, undergoing a vaginal birth. Overall, the included studies were at moderate or low risk of bias, with two trials providing clear information on allocation concealment and blinding. For GRADE outcomes, the certainty of the evidence was generally moderate to high, except from two cases where the certainty of the evidence was either low or very low. High-certainty evidence suggests that intravenous administration of oxytocin in the third stage of labour compared with intramuscular administration carries a lower risk for postpartum haemorrhage (PPH) ≥ 500 mL (average risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92; six trials; 7731 women) and blood transfusion (average RR 0.44, 95% CI 0.26 to 0.77; four trials; 6684 women). Intravenous administration of oxytocin probably reduces the risk of PPH ≥ 1000 mL, although the 95% CI crosses the line of no-effect (average RR 0.65, 95% CI 0.39 to 1.08; four trials; 6681 women; moderate-certainty evidence). In all studies but one, there was a reduction in the risk of PPH ≥ 1000 mL with intravenous oxytocin. The study that found a large increase with intravenous administration was small (256 women), and contributed only 3% of total events. Once this small study was removed from the meta-analysis, heterogeneity was eliminated and the treatment effect favoured intravenous oxytocin (average RR 0.61, 95% CI 0.42 to 0.88; three trials; 6425 women; high-certainty evidence). Additionally, a sensitivity analysis, exploring the effect of risk of bias by restricting analysis to those studies rated as 'low risk of bias' for random sequence generation and allocation concealment, found that the prophylactic administration of intravenous oxytocin reduces the risk for PPH ≥ 1000 mL, compared with intramuscular oxytocin (average RR 0.64, 95% CI 0.43 to 0.94; two trials; 1512 women). The two routes of oxytocin administration may be comparable in terms of additional uterotonic use (average RR 0.78, 95% CI 0.49 to 1.25; six trials; 7327 women; low-certainty evidence). Although intravenous compared with intramuscular administration of oxytocin probably results in a lower risk for serious maternal morbidity (e.g. hysterectomy, organ failure, coma, intensive care unit admissions), the confidence interval suggests a substantial reduction, but also touches the line of no-effect. This suggests that there may be no reduction in serious maternal morbidity (average RR 0.47, 95% CI 0.22 to 1.00; four trials; 7028 women; moderate-certainty evidence). Most events occurred in one study from Ireland reporting high dependency unit admissions, whereas in the remaining three studies there was only one case of uvular oedema. There were no maternal deaths reported in any of the included studies (very low-certainty evidence). There is probably little or no difference in the risk of hypotension between intravenous and intramuscular administration of oxytocin (RR 1.01, 95% CI 0.88 to 1.15; four trials; 6468 women; moderate-certainty evidence). Subgroup analyses based on the mode of administration of intravenous oxytocin (bolus injection or infusion) versus intramuscular oxytocin did not show any substantial differences on the primary outcomes. Similarly, additional subgroup analyses based on whether oxytocin was used alone or as part of active management of the third stage of labour (AMTSL) did not show any substantial differences between the two routes of administration. AUTHORS' CONCLUSIONS: Intravenous administration of oxytocin is more effective than its intramuscular administration in preventing PPH during vaginal birth. Intravenous oxytocin administration presents no additional safety concerns and has a comparable side effects profile with its intramuscular administration. Future studies should consider the acceptability, feasibility and resource use for the intervention, especially in low-resource settings.

Early evaluation of the 'STOP SEPSIS!' WHO Global Maternal Sepsis Awareness Campaign implemented for healthcare providers in 46 low, middle and high-income countries.

OBJECTIVE: To evaluate changes in awareness of maternal sepsis among healthcare providers resulting from the WHO Global Maternal Sepsis Study (GLOSS) awareness campaign. DESIGN: Independent sample precampaign/postcampaign through online and paper-based surveys available for over 30 days before campaign roll-out (pre) and after study data collection (post). Descriptive statistics were used for campaign recognition and exposure, and odds ratio (OR) and percentage change were calculated for differences in awareness, adjusting for confounders using multivariate logistic regression. SETTING AND PARTICIPANTS: Healthcare providers from 398 participating facilities in 46 low, middle and high-income countries. INTERVENTION: An awareness campaign to accompany GLOSS launched 3 weeks prior to data collection and lasting the entire study period (28 November 2017 to 15 January 2018) and beyond. MAIN OUTCOME MEASURES: Campaign recognition and exposure, and changes in awareness. RESULTS: A total of 2188 surveys were analysed: 1155 at baseline and 1033 at postcampaign. Most survey respondents found the campaign materials helpful (94%), that they helped increase awareness (90%) and that they helped motivate to act differently (88%). There were significant changes with regard to: not having heard of maternal sepsis (-63.4% change, pre-OR/post-OR 0.35, 95% CI 0.18 to 0.68) and perception of confidence in making the right decisions with regard to maternal sepsis identification and management (7.3% change, pre-OR/post-OR 1.44, 95% CI 1.01 to 2.06). CONCLUSIONS: Awareness raising campaigns can contribute to an increase in having heard of maternal sepsis and an increase in provider perception of confidence in making correct decisions. Offering the information to make accurate and timely decisions while promoting environments that enable self-confidence and support could improve maternal sepsis identification and management.

Progression of the first stage of spontaneous labour.

This chapter reviews and compiles the most recent published evidence assessing the overall labour duration and patterns of progression for both nulliparous and parous women, as well as the accuracy of the alert and action lines in the World Health Organization (WHO) partograph for the identification of women at risk of birth complications. Systematic reviews of observational studies reporting on the duration of the first and the second stages of labour, and on cervical dilatation patterns for women with low risk of complications with 'normal' perinatal outcomes were identified and updated. The accuracy of the alert (1 cm/h) and action lines of the cervicograph in the partogram to predict adverse birth outcomes among women in first stage of labour was also reviewed, questioning the appropriateness of considering cervical dilatation over time as an isolated indicator to define labour progression or arrest.

Advance misoprostol distribution to pregnant women for preventing and treating postpartum haemorrhage.

BACKGROUND: Advance community distribution of misoprostol for preventing or treating postpartum haemorrhage (PPH) has become an attractive strategy to expand uterotonic coverage to places where conventional uterotonic use is not feasible. However, the value and safety of this strategy remain contentious. This is an update of a Cochrane Review first published in 2012. OBJECTIVES: To assess the effectiveness and safety of the strategy of advance misoprostol distribution to pregnant women for the prevention or treatment of PPH in non-facility births. SEARCH METHODS: For this update, we searched the Cochrane Pregnancy and Childbirth Trial Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (19 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised, cluster-randomised or quasi-randomised controlled trials of advance misoprostol distribution to pregnant women compared with usual (or standard) care for the prevention or treatment of PPH in non-facility births. We excluded studies without any form of random design and those that were available in abstract form only. DATA COLLECTION AND ANALYSIS: At least two review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in included studies. Two review authors independently assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: Two studies conducted in rural Uganda met the inclusion criteria for this review. One was a stepped-wedge cluster-randomised trial (involving 2466 women) which assessed the effectiveness and safety of misoprostol distribution to pregnant women compared with standard care for PPH prevention during non-facility births. The other study (involving 748 women) was a pilot individually randomised placebo-controlled trial which assessed the logistics and feasibility of community antenatal distribution of misoprostol, as well as the effectiveness and safety of self-administration of misoprostol for PPH prevention. Only 271 (11%) of women in the cluster-randomised trial and 299 (40%) of the women in the individually randomised trial had non-facility births. Data from the two studies could not be meta-analysed as the data available from the stepped-wedge trial were not adjusted for the study design. Therefore, the analysed effects of advance misoprostol distribution on PPH prevention largely reflect the findings of the placebo-controlled trial. Neither of the included studies addressed advance misoprostol distribution for the treatment of PPH. Primary outcomes Severe PPH was not reported in the studies. In both the intervention and standard care arms of the two studies, no cases of severe maternal morbidity or death were recorded among women who had a non-facility birth. Secondary outcomes Compared with standard care, it is uncertain whether advance misoprostol distribution has any effect on blood transfusion (no events, 1 study, 299 women), the number of women not using misoprostol (2% in the advance distribution group versus 4% in the usual care group; risk ratio (RR) 0.50, 95% confidence interval (CI) 0.13 to 1.95, 1 study, 299 women), the number of women not using misoprostol correctly (RR 4.86, 95% CI 0.24 to 100.46, 1 study, 290 women), inappropriate use of misoprostol (RR 4.97, 95% CI 0.24 to 102.59, 1 study, 299 women) or maternal transfer or referral to a health facility (RR 0.66, 95% CI 0.11 to 3.91, 1 study, 299 women). Compared with standard care, it is uncertain whether advance misoprostol provision increases the number of women experiencing minor adverse effects: shivering/chills (RR 1.84, CI 95% 1.35 to 2.50, 1 study, 299 women), fever (RR 1.87, 95% CI 1.16 to 3.00, 1 study, 299 women), or diarrhoea (RR 3.92, 95% CI 0.44 to 34.64, 1 study, 299 women); major adverse effects: placenta retention (RR 1.49, 95% CI 0.25 to 8.79, 1 study, 299 women) or hospital admission for longer than 24 hours (RR 0.99, 95% CI 0.66 to 15.73, 1 study, 299 women) after non-facility birth. For all the outcomes included in the 'Summary of findings' table, we assessed the certainty of the evidence as very low, according to GRADE criteria. AUTHORS' CONCLUSIONS: Whilst it might be considered reasonable and feasible to provide advance misoprostol to pregnant women where there are no suitable alternative options for the prevention or treatment of PPH, the evidence on the benefits and harms of this approach remains uncertain. Expansion of uterotonic coverage through this strategy should be cautiously implemented either in the context of rigorous research or with targeted monitoring and evaluation of its impact.

[Omission of causes of maternal death in death certificates in Argentina: nationwide observational studyOmissão do registro de causas maternas de morte na Argentina: estudo observacional de alcance nacional]. / Omisión de registros de causas maternas de muerte en Argentina: estudio observacional de alcance nacional.

OBJECTIVE: To determine the magnitude and characteristics of the omission of causes of maternal death in death certificates in Argentina, and to re-estimate the maternal mortality ratio (MMR) for the year 2014. METHODS: Cross-sectional study. Retrospective review of medical records of women of childbearing age who died from causes suspected of concealing maternal deaths in public, social security, and private institutions in all jurisdictions of the country between 1 January and 31 December 2014. The cause of death recorded in the death certificate was reclassified. Outcome measures included: percentage of records with an omission, structure of causes of death, location, time of death with respect to the reproductive process, and gestational age. The RMM was re-estimated on the basis of the results. RESULTS: Of a sample of 1,176 cases, 969 medical records (82.4%) were analyzed, identifying 60 cases in which the cause of maternal death was omitted (48 maternal deaths, 12 late maternal deaths). Omissions were found in 14.2% of maternal deaths and 33.3% of late maternal deaths. The new estimated MMR for 2014 varied between 43.3 and 47.2 deaths per 100,000 live births. CONCLUSIONS: The omission of causes of maternal death in death certificates in Argentina may be less frequent than international agencies have reported, with differences in omission between regions. Efforts must be made to emphasize the importance of filling out death certificates correctly.

OBJETIVO: Determinar a dimensão e as características da omissão do registro de causas maternas de morte na Argentina e realizar uma nova estimativa da taxa de mortalidade materna (TMM) para o ano 2014. MÉTODOS: Estudo de corte transversal com a revisão retrospectiva dos registros médicos de mulheres em idade reprodutiva que morreram por causas com suspeita de encobrir mortes maternas em instituições da rede pública e previdência social e instituições particulares em todas as jurisdições do país entre 1º. de janeiro e 31 de dezembro de 2014. Foi feita a reclassificação da causa de morte atribuída no Informe Estatístico de Óbitos. As medidas de resultados foram porcentagem de omissão do registro, estrutura de causas de mortes maternas, local, momento da morte em relação ao processo reprodutivo e idade gestacional. Foi realizada uma nova estimativa da TMM com base nos resultados. RESULTADOS: Foram analisados 969 registros médicos (82,4%) de uma amostra de 1.176 casos. Foram identificados 60 casos em que houve omissão da causa materna de morte (48 mortes maternas, 12 mortes maternas tardias). Verificou-se uma porcentagem de omissão de 14,2% para as mortes maternas e 33,3% para as mortes maternas tardias. A nova TMM estimada para o ano 2014 oscilou entre 43,3 e 47,2 mortes por 100.000 nascidos vivos. CONCLUSÕES: A omissão de registro de causas maternas de morte na Argentina pode ser menor que a informada pelas agências internacionais. Existe diferença de omissão entre as regiões. São necessários esforços que enfatizem a importância do preenchimento correto da certidão de óbito.