Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including ...117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I
= 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I
= 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.
Pre-eclampsia Steegers, Eric AP, Prof; von Dadelszen, Peter, MBChB; Duvekot, Johannes J, MD ...
The Lancet (British edition),
08/2010, Letnik:
376, Številka:
9741
Journal Article
Recenzirano
Summary Pre-eclampsia remains a leading cause of maternal and perinatal mortality and morbidity. It is a pregnancy-specific disease characterised by de-novo development of concurrent hypertension and ...proteinuria, sometimes progressing into a multiorgan cluster of varying clinical features. Poor early placentation is especially associated with early onset disease. Predisposing cardiovascular or metabolic risks for endothelial dysfunction, as part of an exaggerated systemic inflammatory response, might dominate in the origins of late onset pre-eclampsia. Because the multifactorial pathogenesis of different pre-eclampsia phenotypes has not been fully elucidated, prevention and prediction are still not possible, and symptomatic clinical management should be mainly directed to prevent maternal morbidity (eg, eclampsia) and mortality. Expectant management of women with early onset disease to improve perinatal outcome should not preclude timely delivery—the only definitive cure. Pre-eclampsia foretells raised rates of cardiovascular and metabolic disease in later life, which could be reason for subsequent lifestyle education and intervention.
Pre‐eclampsia (PE) is a multisystem disorder that typically affects 2%–5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality, especially when the ...condition is of early onset. Globally, 76 000 women and 500 000 babies die each year from this disorder. Furthermore, women in low‐resource countries are at a higher risk of developing PE compared with those in high‐resource countries.
Although a complete understanding of the pathogenesis of PE remains unclear, the current theory suggests a two‐stage process. The first stage is caused by shallow invasion of the trophoblast, resulting in inadequate remodeling of the spiral arteries. This is presumed to lead to the second stage, which involves the maternal response to endothelial dysfunction and imbalance between angiogenic and antiangiogenic factors, resulting in the clinical features of the disorder.
Accurate prediction and uniform prevention continue to elude us. The quest to effectively predict PE in the first trimester of pregnancy is fueled by the desire to identify women who are at high risk of developing PE, so that necessary measures can be initiated early enough to improve placentation and thus prevent or at least reduce the frequency of its occurrence. Furthermore, identification of an “at risk” group will allow tailored prenatal surveillance to anticipate and recognize the onset of the clinical syndrome and manage it promptly.
PE has been previously defined as the onset of hypertension accompanied by significant proteinuria after 20 weeks of gestation. Recently, the definition of PE has been broadened. Now the internationally agreed definition of PE is the one proposed by the International Society for the Study of Hypertension in Pregnancy (ISSHP).
According to the ISSHP, PE is defined as systolic blood pressure at ≥140 mm Hg and/or diastolic blood pressure at ≥90 mm Hg on at least two occasions measured 4 hours apart in previously normotensive women and is accompanied by one or more of the following new‐onset conditions at or after 20 weeks of gestation:
1.Proteinuria (i.e. ≥30 mg/mol protein:creatinine ratio; ≥300 mg/24 hour; or ≥2 + dipstick);
2.Evidence of other maternal organ dysfunction, including: acute kidney injury (creatinine ≥90 μmol/L; 1 mg/dL); liver involvement (elevated transaminases, e.g. alanine aminotransferase or aspartate aminotransferase >40 IU/L) with or without right upper quadrant or epigastric abdominal pain; neurological complications (e.g. eclampsia, altered mental status, blindness, stroke, clonus, severe headaches, and persistent visual scotomata); or hematological complications (thrombocytopenia–platelet count <150 000/μL, disseminated intravascular coagulation, hemolysis); or
3.Uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth).
It is well established that a number of maternal risk factors are associated with the development of PE: advanced maternal age; nulliparity; previous history of PE; short and long interpregnancy interval; use of assisted reproductive technologies; family history of PE; obesity; Afro‐Caribbean and South Asian racial origin; co‐morbid medical conditions including hyperglycemia in pregnancy; pre‐existing chronic hypertension; renal disease; and autoimmune diseases, such as systemic lupus erythematosus and antiphospholipid syndrome. These risk factors have been described by various professional organizations for the identification of women at risk of PE; however, this approach to screening is inadequate for effective prediction of PE.
PE can be subclassified into:
1.Early‐onset PE (with delivery at <34+0 weeks of gestation);
2.Preterm PE (with delivery at <37+0 weeks of gestation);
3.Late‐onset PE (with delivery at ≥34+0 weeks of gestation);
4.Term PE (with delivery at ≥37+0 weeks of gestation).
These subclassifications are not mutually exclusive. Early‐onset PE is associated with a much higher risk of short‐ and long‐term maternal and perinatal morbidity and mortality.
Obstetricians managing women with preterm PE are faced with the challenge of balancing the need to achieve fetal maturation in utero with the risks to the mother and fetus of continuing the pregnancy longer. These risks include progression to eclampsia, development of placental abruption and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. On the other hand, preterm delivery is associated with higher infant mortality rates and increased morbidity resulting from small for gestational age (SGA), thrombocytopenia, bronchopulmonary dysplasia, cerebral palsy, and an increased risk of various chronic diseases in adult life, particularly type 2 diabetes, cardiovascular disease, and obesity. Women who have experienced PE may also face additional health problems in later life, as the condition is associated with an increased risk of death from future cardiovascular disease, hypertension, stroke, renal impairment, metabolic syndrome, and diabetes. The life expectancy of women who developed preterm PE is reduced on average by 10 years. There is also significant impact on the infants in the long term, such as increased risks of insulin resistance, diabetes mellitus, coronary artery disease, and hypertension in infants born to pre‐eclamptic women.
The International Federation of Gynecology and Obstetrics (FIGO) brought together international experts to discuss and evaluate current knowledge on PE and develop a document to frame the issues and suggest key actions to address the health burden posed by PE.
FIGO's objectives, as outlined in this document, are: (1) To raise awareness of the links between PE and poor maternal and perinatal outcomes, as well as to the future health risks to mother and offspring, and demand a clearly defined global health agenda to tackle this issue; and (2) To create a consensus document that provides guidance for the first‐trimester screening and prevention of preterm PE, and to disseminate and encourage its use.
Based on high‐quality evidence, the document outlines current global standards for the first‐trimester screening and prevention of preterm PE, which is in line with FIGO good clinical practice advice on first trimester screening and prevention of pre‐eclampsia in singleton pregnancy.1
It provides both the best and the most pragmatic recommendations according to the level of acceptability, feasibility, and ease of implementation that have the potential to produce the most significant impact in different resource settings. Suggestions are provided for a variety of different regional and resource settings based on their financial, human, and infrastructure resources, as well as for research priorities to bridge the current knowledge and evidence gap.
To deal with the issue of PE, FIGO recommends the following:
Public health focus: There should be greater international attention given to PE and to the links between maternal health and noncommunicable diseases (NCDs) on the Sustainable Developmental Goals agenda. Public health measures to increase awareness, access, affordability, and acceptance of preconception counselling, and prenatal and postnatal services for women of reproductive age should be prioritized. Greater efforts are required to raise awareness of the benefits of early prenatal visits targeted at reproductive‐aged women, particularly in low‐resource countries.
Universal screening: All pregnant women should be screened for preterm PE during early pregnancy by the first‐trimester combined test with maternal risk factors and biomarkers as a one‐step procedure. The risk calculator is available free of charge at https://fetalmedicine.org/research/assess/preeclampsia. FIGO encourages all countries and its member associations to adopt and promote strategies to ensure this. The best combined test is one that includes maternal risk factors, measurements of mean arterial pressure (MAP), serum placental growth factor (PLGF), and uterine artery pulsatility index (UTPI). Where it is not possible to measure PLGF and/or UTPI, the baseline screening test should be a combination of maternal risk factors with MAP, and not maternal risk factors alone. If maternal serum pregnancy‐associated plasma protein A (PAPP‐A) is measured for routine first‐trimester screening for fetal aneuploidies, the result can be included for PE risk assessment. Variations to the full combined test would lead to a reduction in the performance screening. A woman is considered high risk when the risk is 1 in 100 or more based on the first‐trimester combined test with maternal risk factors, MAP, PLGF, and UTPI.
Contingent screening: Where resources are limited, routine screening for preterm PE by maternal factors and MAP in all pregnancies and reserving measurements of PLGF and UTPI for a subgroup of the population (selected on the basis of the risk derived from screening by maternal factors and MAP) can be considered.
Prophylactic measures: Following first‐trimester screening for preterm PE, women identified at high risk should receive aspirin prophylaxis commencing at 11–14+6 weeks of gestation at a dose of ~150 mg to be taken every night until 36 weeks of gestation, when delivery occurs, or when PE is diagnosed. Low‐dose aspirin should not be prescribed to all pregnant women. In women with low calcium intake (<800 mg/d), either calcium replacement (≤1 g elemental calcium/d) or calcium supplementation (1.5–2 g elemental calcium/d) may reduce the burden of both early‐ and late‐onset PE.
Objective
To determine the relative burdens of maternal and perinatal complications for preterm and term pre‐eclampsia.
Design
Prospective observational cohort study.
Setting
Two English maternity ...units.
Population
Unselected women with singleton pregnancies who developed pre‐eclampsia (International Society for the Study of Hypertension in Pregnancy definition).
Methods
Outcomes were ascertained by health record review and compared between pregnancies with preterm (versus term) pre‐eclampsia.
Main outcome measures
Severe maternal hypertension, maternal mortality or major maternal morbidity, perinatal mortality or major neonatal morbidity, neonatal unit (NNU) admission ≥48 hours, and birthweight <3rd percentile.
Results
Among 40 241 singleton pregnancies, 298 (0.7%, 95% confidence interval CI 0.66–0.83) and 1194 (3.0%, 95% CI 2.8–3.1) developed preterm and term pre‐eclampsia, respectively. Women with preterm (versus term) pre‐eclampsia more commonly experienced adverse maternal or perinatal events: severe hypertension 18.5% (95% CI 14.5–23.3) versus 13.6% (95% CI 11.7–15.6); maternal mortality/major morbidity 7.4% (95% CI 4.9–10.9) versus 2.2% (95% CI 1.5–3.2); perinatal mortality/major neonatal morbidity 29.5% (95% CI 24.6–34.9) versus 2.2% (95% CI 1.5–3.2); and birthweight <3rd percentile 54.4% (95% CI 48.7–59.9) versus 14.2% (95% CI 12.4–16.3). However, in absolute terms, most maternal complications occurred in women with term pre‐eclampsia, as did a large proportion of perinatal complications: severe hypertension 74.7% (95% CI 68.5–80.0); maternal mortality/major morbidity 54.2% (95% CI 40.3–67.4); perinatal mortality/major neonatal morbidity 22.8% (95% CI 16.1–31.3); NNU admission ≥48 hours 38.1% (95% CI 32.4–44.1); and birthweight <3rd percentile 51.2% (95% CI 45.8–56.5).
Conclusions
Although adverse event risks are greater with preterm (versus term) pre‐eclampsia, term disease is associated with at least equivalent total numbers of maternal, and a significant proportion of perinatal, adverse events. Increased efforts should be made to decrease the incidence of term pre‐eclampsia.
This article includes Author Insights, a video presented by Laura A. Magee available at: https://vimeo.com/790715868
The COVID-19 pandemic has had a profound impact on health-care systems and potentially on pregnancy outcomes, but no systematic synthesis of evidence of this effect has been undertaken. We aimed to ...assess the collective evidence on the effects on maternal, fetal, and neonatal outcomes of the pandemic.
We did a systematic review and meta-analysis of studies on the effects of the pandemic on maternal, fetal, and neonatal outcomes. We searched MEDLINE and Embase in accordance with PRISMA guidelines, from Jan 1, 2020, to Jan 8, 2021, for case-control studies, cohort studies, and brief reports comparing maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. We also planned to record any additional maternal and offspring outcomes identified. Studies of solely SARS-CoV-2-infected pregnant individuals, as well as case reports, studies without comparison groups, narrative or systematic literature reviews, preprints, and studies reporting on overlapping populations were excluded. Quantitative meta-analysis was done for an outcome when more than one study presented relevant data. Random-effects estimate of the pooled odds ratio (OR) of each outcome were generated with use of the Mantel-Haenszel method. This review was registered with PROSPERO (CRD42020211753).
The search identified 3592 citations, of which 40 studies were included. We identified significant increases in stillbirth (pooled OR 1·28 95% CI 1·07–1·54; I2=63%; 12 studies, 168 295 pregnancies during and 198 993 before the pandemic) and maternal death (1·37 1·22–1·53; I2=0%, two studies both from low-income and middle-income countries, 1 237 018 and 2 224 859 pregnancies) during versus before the pandemic. Preterm births before 37 weeks' gestation were not significantly changed overall (0·94 0·87–1·02; I2=75%; 15 studies, 170 640 and 656 423 pregnancies) but were decreased in high-income countries (0·91 0·84–0·99; I2=63%; 12 studies, 159 987 and 635 118 pregnancies), where spontaneous preterm birth was also decreased (0·81 0·67–0·97; two studies, 4204 and 6818 pregnancies). Mean Edinburgh Postnatal Depression Scale scores were higher, indicating poorer mental health, during versus before the pandemic (pooled mean difference 0·42 95% CI 0·02–0·81; three studies, 2330 and 6517 pregnancies). Surgically managed ectopic pregnancies were increased during the pandemic (OR 5·81 2·16–15·6; I2=26%; three studies, 37 and 272 pregnancies). No overall significant effects were identified for other outcomes included in the quantitative analysis: maternal gestational diabetes; hypertensive disorders of pregnancy; preterm birth before 34 weeks', 32 weeks', or 28 weeks' gestation; iatrogenic preterm birth; labour induction; modes of delivery (spontaneous vaginal delivery, caesarean section, or instrumental delivery); post-partum haemorrhage; neonatal death; low birthweight (<2500 g); neonatal intensive care unit admission; or Apgar score less than 7 at 5 min.
Global maternal and fetal outcomes have worsened during the COVID-19 pandemic, with an increase in maternal deaths, stillbirth, ruptured ectopic pregnancies, and maternal depression. Some outcomes show considerable disparity between high-resource and low-resource settings. There is an urgent need to prioritise safe, accessible, and equitable maternity care within the strategic response to this pandemic and in future health crises.
None.
Preeclampsia Magee, Laura A.; Nicolaides, Kypros H.; von Dadelszen, Peter
The New England journal of medicine,
05/2022, Letnik:
386, Številka:
19
Journal Article
Recenzirano
Preeclampsia complicates 2 to 4% of all pregnancies and accounts for about 46,000 maternal deaths and 500,000 fetal or newborn deaths each year. Antihypertensive agents and magnesium sulfate can help ...control the systemic manifestations of preeclampsia, which is usually resolved by delivery of the placenta.
laura.a.magee@kcl.ac.uk The recent UK Obstetric Surveillance System (UKOSS) study provides UK specific information about covid-19 in pregnancy.1 Women’s symptoms, risk factors for severe disease, and ...gestational age at presentation with covid-19, as well as increased preterm birth and caesarean delivery rates, are consistent with global data (systematic review and meta-analysis of 86 studies, including UKOSS, up to 8 June 2020).2 However, UKOSS has documented two findings that warrant emphasis. ...UKOSS data show an incidence of stillbirth (11.5 per 1000 total births) among women affected by covid-19 that is almost three times the national rate (4.1 per 1000 total births)3 when the standard denominator used is completed maternities (n=262). ...antiviral drugs were used less often in the UK (in 2% (9/247) of women compared with a median of 18%).2 One woman in the UKOSS study received lopinavir-ritonavir, so some pregnant women seem to have been enrolled in the RECOVERY trial launched in the UK on 24 March 2020.
This study compares pregnancy outcomes, including rates of stillbirth (fetal death ≥24 weeks' gestation), preterm and cesarean delivery, and neonatal unit admission in the months preceding vs during ...the 2020 COVID-19 pandemic at a London university hospital.
Objective
To examine the effect of self‐declared race on serum placental growth factor (PlGF) and sFlt‐1/PlGF ratio and the impact on pre‐eclampsia (PE) prediction.
Design
Prospective observational ...study.
Setting
Two UK maternity hospitals.
Population
29 035 women with singleton pregnancies attending a routine 35+0 to 36+6 weeks' gestation hospital visit, including 654 (2.3%) who subsequently developed PE.
Methods
The predictive performance of PlGF and sFlt‐1/PlGF for PE in minority racial groups (versus white) was examined.
Main outcome measure
Delivery with PE.
Results
Compared with white women, mean PlGF was higher and sFlt‐1/PlGF ratio lower in black, South Asian, East Asian and mixed race women. In white women at a PlGF concentration cut‐off corresponding to a screen‐positive rate (SPR) of 10%, detection rates (DRs) were 49.1% for PE at any time and 72.3% for PE within 2 weeks after screening. In black women, at the same PlGF concentration cut‐off for white women, the SPR was 5.5%, and DRs 33.6% and 55.0%, respectively; the number of PE cases was too small to evaluate screening performance in other racial groups. Using a fixed cut‐off in sFlt‐1/PlGF ratio to identify women at risk of developing PE, similarly diagnostically disadvantaged black women. Bias was overcome by adjusting metabolite concentrations for maternal characteristics and use of the competing risks model to estimate patient‐specific risks.
Conclusion
Screening for PE with fixed cut‐offs in PlGF or sFlt‐1/PlGF diagnostically disadvantages black women. It is essential that measured levels of PlGF be adjusted for race as well as other maternal characteristics.
Linked article: This article is commented on by Philip J. Steer, pp. 88 in this issue. To view this mini commentary visit https://doi.org/10.1111/1471-0528.17305.
In this trial comparing less-tight control of hypertension (target diastolic blood pressure, 100 mm Hg) with tight control (85 mm Hg) among pregnant women, rates of pregnancy loss, high-level ...neonatal care, and serious maternal complications were similar between groups.
Almost 10% of pregnant women have hypertension; hypertension is preexisting in 1%, gestational hypertension without proteinuria develops in 5 to 6%, and preeclampsia develops in 2%.
1
Preexisting hypertension and gestational hypertension before 34 weeks are associated with an increased risk of perinatal and maternal complications.
2
–
4
Blood-pressure targets for women with nonsevere hypertension during pregnancy are much debated. Relevant randomized, controlled trials have been small and of moderate or poor quality; tight control (the use of antihypertensive therapy to normalize blood pressure) has been associated with maternal benefits (e.g., a decrease in the frequency of severe hypertension and possibly in . . .
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