Perspectives on administration of COVID-19 vaccine to pregnant and lactating women: a challenge for low- and middle-income countries.

Women who are in the pregnancy-puerperal cycle or are lactating have been deliberately excluded from participating in COVID-19 vaccine clinical trials that aimed to evaluate either the efficacy of the vaccines in inducing the formation of neutralizing antibodies or the investigational products' safety profile. The exclusion of pregnant and lactating women from such studies certainly and inequitably denies these women access to COVID-19 vaccines, since these products have become increasingly available to nonpregnant people and even to those who are pregnant and are in high-income settings. In this clinical opinion article, we discuss some aspects of the prolonged pandemic, the emergence of viral variants, the risks of severe complications of COVID-19 in pregnant women, and the disproportionate impact of the above on low- and middle-income countries. We argue that the decision to receive the COVID-19 vaccine should be a joint decision between the pregnant or lactating women and the healthcare providers, while considering the available data on vaccine efficacy, safety, the risks of SARS-CoV-2 infection in pregnant women, and the women's individual risks for infection and serious illness. The various types of vaccines that are already in use and their safety, effectiveness, and the potential risks and benefits of their administration to pregnant or lactating women are also reviewed.

Magnetic resonance imaging of skull and brain parameters in fetuses with intrauterine growth restriction.

OBJECTIVE: To compare fetuses with intrauterine growth restriction (IUGR) and those with normal growth, in terms of skull and brain measurements obtained by magnetic resonance imaging (MRI). MATERIALS AND METHODS: This was a prospective cohort study including 26 single fetuses (13 with IUGR and 13 with normal growth), evaluated from 26 to 38 weeks of gestation. Using MRI, we measured skull and brain biparietal diameters (BPDs); skull and brain occipitofrontal diameters (OFDs); corpus callosum length and area; transverse cerebellar diameter; extracerebral cerebrospinal fluid (eCSF); and right and left interopercular distances (IODs). RESULTS: The following were significantly smaller in IUGR fetuses than in control fetuses: skull BPD (76.9 vs. 78.2 mm; p = 0.0029); brain BPD (67.8 vs. 71.6 mm; p = 0.0064); skull OFD (93.6 vs. 95 mm; p = 0.0010); eCSF (5.5 vs. 8.2 mm; p = 0.0003); right IOD (9.8 vs. 13.9 mm; p = 0.0023); and left IOD (11.8 vs. 16.3 mm; p = 0.0183). The skull BPD/eCSF, brain BPD/eCSF, skull OFD/eCSF, and brain OFD/eCSF ratios were also lower in IUGR fetuses. CONCLUSION: IUGR fetuses had smaller OFD and BPD, both skull and brain, and less eCSF when compared to normal growth fetuses.

OBJETIVO: Comparar medidas do crânio e encéfalo por meio da ressonância magnética (RM) de fetos com restrição do crescimento intrauterino (RCIU) e com crescimento adequado. MATERIAIS E MÉTODOS: Realizou-se um estudo de coorte prospectivo com 13 fetos com RCIU e 13 controles entre 26 e 38 semanas. Foram realizadas as seguintes medidas por RM: diâmetro biparietal (DBP) e diâmetro occipitofrontal (DOF) cerebral e ósseo, comprimento e área do corpo caloso (CPC), diâmetro transverso do cerebelo, líquido cerebroespinhal (LCE) extracerebral e distância interopercular (DIO) direita e esquerda. RESULTADOS: Observaram-se diferenças significativas nas medidas do DBP ósseo (76,9 vs. 78,2 mm; p = 0,0029), DBP cerebral (67,8 vs. 71,6 mm; p = 0,0064) e DOF ósseo (93,6 vs. 95 mm; p = 0,0010) em fetos com RCIU em relação aos fetos com crescimento normal. Observaram-se, ainda, diferenças significativas nas médias do LCE extracerebral (5,5 vs. 8,2 mm; p = 0,0003) e DIO direita (9,8 vs. 13,9 mm; p = 0,0023) e esquerda (11,8 vs. 16,3 mm; p = 0,0183) em fetos com RCIU em relação aos controles. Fetos com RCIU e normais tiveram diferenças entre DBP ósseo/LCE, DBP cerebral/LCE, DOF/LEC, e DOF cerebral/LCE. CONCLUSÃO: Fetos com RCIU tiveram menores DBP e DOF, ambos crânio e encéfalo, e menor LCE extracerebral que fetos com crescimento adequado.

Previous preeclampsia and its association with the future development of cardiovascular diseases: a systematic review and meta-analysis.

Preeclampsia is a multifactorial disease. Among these factors, untreated hypertension during pregnancy can result in high morbidity and mortality rates and may also be related to the future development of cardiovascular diseases.Therefore, this systematic review aimed to determine the association of previous preeclampsia with the future development of cardiovascular diseases. Studies on the association between preeclampsia and future cardiovascular diseases published in the last 10 years (2009-2019) were identified from the PubMed/Medline (207 articles), Embase (nine articles), and Cochrane (three articles) databases using the keywords "preeclampsia" and "future cardiovascular diseases", "preeclampsia" and "future heart attack", and "preeclampsia" and "future cardiac disease". After applying the inclusion and exclusion criteria, 15 articles were analyzed by systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis and the determination of the quality of the articles were conducted using RevMan software, version 5.3. Statistically significant differences were observed between the control and previous preeclampsia groups with respect to systolic blood pressure (mean difference [MD] 4.32; 95% confidence interval [95%CI] 3.65, 4.99; p<0.001), diastolic blood pressure (MD): 2.11; 95%CI: 1.68, 2.55; p<0.0001), and insulin level (MD: 2.80; 95% CI: 0.50, 5.11; p<0.001). Body mass index (MD: 2.57, 95%CI: 2.06, 3.07; p=0.0001), total cholesterol (MD: 10.39; 95%CI: 8.91, 11.87; p=0.0001), HDL (MD: 2.83; 95%CI: 2.20, 3.46; p=0.0001), and LDL (MD: 1.77; 95%CI: 0.42, 3.13; p=0.0001) also differed significantly between groups. Thus, the results of the present study showed that women with a history of preeclampsia were more likely to develop cardiovascular disease.

Previous preeclampsia and its association with the future development of cardiovascular diseases: a systematic review and meta-analysis

Preeclampsia is a multifactorial disease. Among these factors, untreated hypertension during pregnancy can result in high morbidity and mortality rates and may also be related to the future development of cardiovascular diseases.Therefore, this systematic review aimed to determine the association of previous preeclampsia with the future development of cardiovascular diseases. Studies on the association between preeclampsia and future cardiovascular diseases published in the last 10 years (2009-2019) were identified from the PubMed/Medline (207 articles), Embase (nine articles), and Cochrane (three articles) databases using the keywords "preeclampsia" and "future cardiovascular diseases", "preeclampsia" and "future heart attack", and "preeclampsia" and "future cardiac disease". After applying the inclusion and exclusion criteria, 15 articles were analyzed by systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis and the determination of the quality of the articles were conducted using RevMan software, version 5.3. Statistically significant differences were observed between the control and previous preeclampsia groups with respect to systolic blood pressure (mean difference [MD] 4.32; 95% confidence interval [95%CI] 3.65, 4.99; p<0.001), diastolic blood pressure (MD): 2.11; 95%CI: 1.68, 2.55; p<0.0001), and insulin level (MD: 2.80; 95% CI: 0.50, 5.11; p<0.001). Body mass index (MD: 2.57, 95%CI: 2.06, 3.07; p=0.0001), total cholesterol (MD: 10.39; 95%CI: 8.91, 11.87; p=0.0001), HDL (MD: 2.83; 95%CI: 2.20, 3.46; p=0.0001), and LDL (MD: 1.77; 95%CI: 0.42, 3.13; p=0.0001) also differed significantly between groups. Thus, the results of the present study showed that women with a history of preeclampsia were more likely to develop cardiovascular disease.

SARS-CoV-2 and Pregnancy: A Review of the Facts.

OBJECTIVE: The present comprehensive review aims to show the full extent of what is known to date and provide a more thorough view on the effects of SARS-CoV2 in pregnancy. METHODS: Between March 29 and May, 2020, the words COVID-19, SARS-CoV2, COVID-19 and pregnancy, SARS-CoV2 and pregnancy, and SARS and pregnancy were searched in the PubMed and Google Scholar databases; the guidelines from well-known societies and institutions (Royal College of Obstetricians and Gynaecologists [RCOG], American College of Obstetricians and Gynecologists [ACOG], International Society of Ultrasound in Obstetrics & Gynecology [ISUOG], Centers for Disease Control and Prevention [CDC], International Federation of Gynecology and Obstetrics [FIGO]) were also included. CONCLUSION: The COVID-19 outbreak resulted in a pandemic with > 3.3 million cases and 230 thousand deaths until May 2nd. It is caused by the SARS-CoV2 virus and may lead to severe pulmonary infection and multi-organ failure. Past experiences show that unique characteristics in pregnancy make pregnant women more susceptible to complications from viral infections. Yet, this has not been reported with this new virus. There are risk factors that seem to increase morbidity in pregnancy, such as obesity (body mass index [BMI] > 35), asthma and cardiovascular disease. Current reports describe an increased rate of preterm birth and C-section. Vertical transmission is still a possibility, due to a few reported cases of neonatal positive real-time polymerase chain reaction (RT-PCR) in nasal swab, amniotic fluid, and positive immunoglobulin M (IgM) in neonatal blood. Treatments must be weighed in with caution due to the lack of quality trials that prove their effectiveness and safety during pregnancy. Medical staff must use personal protective equipment in handling SARS-CoV2 suspected or positive patients and be alert for respiratory decompensations.

OBJETIVO: A presente revisão detalhada busca fornecer dados objetivos para avaliar o que se sabe até o momento e possibilitar uma visão mais ampla dos efeitos do SARS-CoV2 na gravidez. MéTODOS: Entre 29 de março e 2 de maio de 2020, foi realizada uma busca nos bancos de dados PubMed e Google Scholar com as palavras COVID-19, SARS-CoV2, COVID-19 e gravidez, SARS-CoV2 e gravidez, e SARS e gravidez. As recomendações dos principais órgãos sobre o tema também foram acessadas. CONCLUSãO: O surto de COVID-19 resultou em uma pandemia com > 3.3 milhões de casos e 230 mil mortes até 2 de maio. É uma condição causada pelo vírus SARS-CoV2 e pode levar ao acometimento pulmonar difuso e à falência de múltiplos órgãos. Características únicas da gestante tornam essa população mais propensas a complicações de infecções virais. Até o momento, essa tendência não foi observada para esse novo vírus. Os fatores que parecem estar associados à maior morbidade materno-fetal são obesidade (índice de massa corporal [IMC] > 35), asma e doença cardiovascular. Há descrição de aumento de parto prematuro e parto cesáreo. Não se pode descartar a possibilidade de transmissão vertical da doença, devido a relatos de positividade de reação em cadeia de polimerase (RT-PCR) de swab nasal, RT-PCR de líquido amniótico e imunoglobulina M (IgM) de recém-nascidos. Tratamentos devem ser analisados caso a caso, dada a falta de qualidade de estudos que comprovem a sua eficácia e segurança na gravidez. O corpo clínico deve utilizar equipamentos de proteção individual (EPI) ao manusear pacientes suspeitos ou confirmados e ficar atento aos sinais de descompensação respiratória.

A minimum estimate of the prevalence of 22q11 deletion syndrome and other chromosome abnormalities in a combined prenatal and postnatal cohort.

STUDY QUESTION: What is the frequency of major chromosome abnormalities in a population-based diagnostic data set of genomic tests performed on miscarriage, fetal and infant samples in a state with >73 000 annual births? SUMMARY ANSWER: The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826), with a significant decrease in the detection of major chromosome abnormalities with later developmental stage, from 50.9% to 21.3% to 15.6% of tests in the miscarriage, prenatal and postnatal cohorts, respectively. WHAT IS KNOWN ALREADY: Over the past decade, technological advances have revolutionized genomic testing at every stage of reproduction. Chromosomal microarrays (CMAs) are now the gold standard of chromosome assessment in prenatal diagnosis and pediatrics. STUDY DESIGN, SIZE, DURATION: A population-based cohort study including all chromosome analysis was performed in the Australian state of Victoria during a 24-month period from January 2015 to December 2016. All samples obtained via invasive prenatal diagnosis and postnatal samples from pregnancy tissue and infants ≤12 months of age were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A research collaboration of screening and diagnostic units in the Australian state of Victoria was formed (the Perinatal Record Linkage collaboration), capturing all instances of prenatal and postnatal chromosome testing performed in the state. Victoria has over 73 000 births per annum and a median maternal age of 31.5 years. We analyzed our population-based diagnostic data set for (i) chromosome assessment of miscarriage, prenatal diagnosis and postnatal samples; (ii) testing indications and diagnostic yields for each of these cohorts; (iii) and the combined prenatal/infant prevalence of 22q11.2 deletion syndrome (DS) as a proportion of all births ≥20 weeks gestation. MAIN RESULTS AND THE ROLE OF CHANCE: During the 24-month study period, a total of 8826 chromosomal analyses were performed on prenatal and postnatal specimens in Victoria. The vast majority (91.2%) of all chromosome analyses were performed with CMA.The overall frequency of major chromosome abnormalities in the entire cohort was 28.2% (2493/8826). There was a significant decreasing trend in the percentage of chromosome abnormalities with later developmental stage from 50.9% to 21.3% to 15.6% in the miscarriage, prenatal and postnatal cohorts, respectively (χ2 trend = 790.0, P < 0.0001). The total frequency of abnormalities in the live infant subgroup was 13.4% (244/1816). The frequencies of pathogenic copy number variants (CNVs) detected via CMA for the miscarriage, prenatal and postnatal cohorts were 1.9% (50/2573), 2.2% (82/3661) and 4.9% (127/2592), respectively. There was a significant increasing trend in the frequency of pathogenic CNVs with later developmental stage (χ2 trend = 39.72, P < 0.0001). For the subgroup of live infants, the pathogenic CNV frequency on CMA analysis was 6.0% (109/1816). There were 38 diagnoses of 22q11.2 DS, including 1 miscarriage, 15 prenatal and 22 postnatal cases. After excluding the miscarriage case and accounting for duplicate testing, the estimated prevalence of 22q11 DS was 1 in 4558 Victorian births. LIMITATIONS, REASONS FOR CAUTION: Clinical information was missing on 11.6% of postnatal samples, and gestational age was rarely provided on the miscarriage specimens. We were unable to obtain rates of termination of pregnancy and stillbirth in our cohort due to incomplete data provided by clinical referrers. We therefore cannot make conclusions on pregnancy or infant outcome following diagnostic testing. Childhood and adult diagnoses of 22q11 DS were not collected. WIDER IMPLICATIONS OF THE FINDINGS: Our study marks a complete transition in genomic testing from the G-banded karyotype era, with CMA now established as the first line investigation for pregnancy losses, fetal diagnosis and newborn/infant assessment in a high-income setting. Integration of prenatal and postnatal diagnostic data sets provides important opportunities for estimating the prevalence of clinically important congenital syndromes, such as 22q11 DS. STUDY FUNDING/COMPETING INTEREST(S): L.H. is funded by a National Health and Medical Research Council Early Career Fellowship (1105603); A.L. was funded by a Mercy Perinatal Research Fellowship; J.H. was funded by a National Health and Medical Research Council Senior Research Fellowship (10121252). The funding bodies had no role in the conduct of the research or the manuscript. Discretionary funding from the Murdoch Children's Research Institute has supported the prenatal diagnosis data collection and reporting over the years.Dr Ricardo Palma-Dias reports a commercial relationship with Roche Diagnostics, personal fees from Philips Ultrasound, outside the submitted work. Debbie Nisbet reports a commercial relationship with Roche Diagnostics, outside the submitted work. TRIAL REGISTRATION NUMBER: NA.

Treatment of severe hypertension during pregnancy: we still do not know what the best option is.

Intracranial hemorrhage and stroke are primary causes of maternal mortality in pregnancies affected by hypertensive disorders. As such antihypertensive therapy plays a crucial role in the management of severe hypertension. However, the target level to achieve the best outcome for both - mother and fetus - is still unclear. Moreover, given the lack of well-designed randomized controlled trials with standardized key outcomes, the current choice of antihypertensive medications depends rather on clinicians' preference. Furthermore, data on long-term outcomes of offspring is not available. Therefore, there is an urgent need for randomized trials comparing different anti-hypertensive options to address efficacy and safety questions.

Análise de impacto orçamentário do uso da razão dos testes sFlt-1: PlGF na exclusão de pré-eclâmpsia em mulheres com suspeita clínica na perspectiva do sistema de saúde suplementar / Budget impact analysis of sFlt-1/PlGF ratio to help rule-out pre-eclampsia in women presenting with clinical suspected in the private healthcare system perspective in Brazil

Objetivo: O objetivo do estudo foi avaliar o impacto econômico da incorporação da razão dos testes tirosina quinase-1 solúvel (sFlt-1):fator de crescimento placentário (PlGF) no auxílio da exclusão da pré-eclâmpsia na perspectiva do Sistema de Saúde Suplementar do Brasil (SSS). Métodos: Foi desenvolvido um modelo de decisão com o intuito de simular as decisões clínicas do manejo das pacientes com suspeita de pré-eclâmpsia entre a 24ª semana e a 36ª semana + 6 dias de gestação utilizando a razão dos testes sFlt-1:PlGF em comparação com cenário sem o teste. Os dados clínicos utilizados no modelo foram derivados do estudo PROGNOSIS. A análise incluiu apenas custos diretos que foram baseados na Tabela CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) e na Tabela CMED PF 18% (Câmara de Regulação do Mercado de Medicamentos). Uma análise de sensibilidade univariada foi conduzida com variação de 15% dos parâmetros. Resultados: A razão dos testes sFlt-1:PlGF apresentou um potencial de economia de -R$ 4.532,04 por paciente comparado ao cenário sem teste. Considerando a incorporação no SSS, a razão dos testes sFlt-1:PlGF pode promover uma economia de -R$ 6.375.865,68 em 2021 e um acumulado de -R$ 136.495.533,87 em cinco anos. Conclusão: O uso da razão sFlt-1:PlGF no auxílio da exclusão da pré-eclâmpsia tem potencial de melhorar as decisões clínicas e, consequentemente, evitar hospitalizações desnecessárias. A incorporação do teste pode promover uma economia substancial para o sistema de saúde suplementar

Objective: The aim of this study was to evaluate the economic impact of the incorporation of the soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PlGF) ratio test in the private healthcare system in Brazil (SSS). Methods: A decision model was developed in order to simulate the clinical decisions of the management of women with suspected pre-eclampsia between 24 weeks and 36 weeks plus 6 days with sFlt-1:PlGF ratio test, compared with no test scenario. The clinical data used in the model were derived from PROGNOSIS study. The analysis included only direct costs that were based on CBHPM (Classificação Brasileira Hierarquizada de Procedimentos Médicos) and CMED PF 18% (Câmara de Regulação do Mercado de Medicamentos). A univariate sensitivity analysis was conducted with a variation of 15%. Results: The sFlt-1:PlGF ratio test has the potential to save -R$ 4.532,04 per patient compared to no test scenario. Considering the incorporation of the test in SSS, the sFlt1:PlGF ratio test can promote an economy of -R$ 6.375.865,68 in 2021 and -R$ 136.495.533,87 in accumulated five years of. Conclusion: The use of sFlt-1:PlGF ratio test to help rule-out pre-eclampsia has the potential to improve clinical decision and therefore to reduce unnecessary hospitalizations. The incorporation of the test can promote a substantial saving to the private healthcare system.