Publications by authors named "Asma Khalil"

265 Publications

Erratum to systematic review and critical evaluation of quality of clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy.

Am J Obstet Gynecol MFM 2022 Aug 5:100683. Epub 2022 Aug 5.

Department of Obstetrics and Gynecology, Center for Fetal Care and High-Risk Pregnancy, University of Chieti, Chieti, Italy (Drs Di Girolamo, Capannolo, Buca, Liberati, and D'Antonio). Electronic address:

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http://dx.doi.org/10.1016/j.ajogmf.2022.100683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355748PMC
August 2022

Gestational age at birth and outcome in monochorionic twins with different types of selective fetal growth restriction: A systematic literature review.

Prenat Diagn 2022 Jul 8. Epub 2022 Jul 8.

Department of Pediatrics, Neonatology, Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, The Netherlands.

This systematic review aims to assess the gestational age at birth and perinatal outcome [intrauterine demise (IUD), neonatal mortality and severe cerebral injury] in monochorionic twins with selective fetal growth restriction (sFGR), according to Gratacós classification based on umbilical artery Doppler flow patterns in the smaller twin. Seventeen articles were included. Gestational age at birth varied from 33.0 to 36.0 weeks in type I, 27.6-32.4 weeks in type II, and 28.3-33.8 weeks in type III. IUD rate differed from 0%-4% in type I to 0%-40% in type II and 0%-23% in type III. Neonatal mortality rate was between 0%-10% in type I, 0%-38% in type II, and 0%-17% in type III. Cerebral injury was present in 0%-2% of type I, 2%-30% of type II and 0%-33% of type III cases. The timing of delivery in sFGR varied substantially among studies, particularly in type II and III. The quality of evidence was moderate due to heterogenous study populations with varying definitions of sFGR and perinatal outcome parameters, as well as a lack of consensus on the use of the Gratacós classification, leading to substantial incomparability. Our review identifies the urgent need for uniform antenatal diagnostic criteria and definitions of outcome parameters.
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http://dx.doi.org/10.1002/pd.6206DOI Listing
July 2022

Monkeypox vaccines in pregnancy: lessons must be learned from COVID-19.

Lancet Glob Health 2022 Sep 27;10(9):e1230-e1231. Epub 2022 Jun 27.

Paediatric Infectious Diseases Research Group and Vaccine Institute, Institute of Infection and Immunity, St George's University of London, London, UK; Immunisation and Countermeasures Division, Public Health England, London, UK; British Paediatric Surveillance Unit, Royal College of Paediatrics and Child Health, London, UK.

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http://dx.doi.org/10.1016/S2214-109X(22)00284-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236565PMC
September 2022

Evaluation of the Growth Assessment Protocol (GAP) for antenatal detection of small for gestational age: The DESiGN cluster randomised trial.

PLoS Med 2022 06 21;19(6):e1004004. Epub 2022 Jun 21.

Department of Women and Children's Health, King's College London, London, United Kingdom.

Background: Antenatal detection and management of small for gestational age (SGA) is a strategy to reduce stillbirth. Large observational studies provide conflicting results on the effect of the Growth Assessment Protocol (GAP) in relation to detection of SGA and reduction of stillbirth; to the best of our knowledge, there are no reported randomised control trials. Our aim was to determine if GAP improves antenatal detection of SGA compared to standard care.

Methods And Findings: This was a pragmatic, superiority, 2-arm, parallel group, open, cluster randomised control trial. Maternity units in England were eligible to participate in the study, except if they had already implemented GAP. All women who gave birth in participating clusters (maternity units) during the year prior to randomisation and during the trial (November 2016 to February 2019) were included. Multiple pregnancies, fetal abnormalities or births before 24+1 weeks were excluded. Clusters were randomised to immediate implementation of GAP, an antenatal care package aimed at improving detection of SGA as a means to reduce the rate of stillbirth, or to standard care. Randomisation by random permutation was stratified by time of study inclusion and cluster size. Data were obtained from hospital electronic records for 12 months prerandomisation, the washout period (interval between randomisation and data collection of outcomes), and the outcome period (last 6 months of the study). The primary outcome was ultrasound detection of SGA (estimated fetal weight <10th centile using customised centiles (intervention) or Hadlock centiles (standard care)) confirmed at birth (birthweight <10th centile by both customised and population centiles). Secondary outcomes were maternal and neonatal outcomes, including induction of labour, gestational age at delivery, mode of birth, neonatal morbidity, and stillbirth/perinatal mortality. A 2-stage cluster-summary statistical approach calculated the absolute difference (intervention minus standard care arm) adjusted using the prerandomisation estimate, maternal age, ethnicity, parity, and randomisation strata. Intervention arm clusters that made no attempt to implement GAP were excluded in modified intention to treat (mITT) analysis; full ITT was also reported. Process evaluation assessed implementation fidelity, reach, dose, acceptability, and feasibility. Seven clusters were randomised to GAP and 6 to standard care. Following exclusions, there were 11,096 births exposed to the intervention (5 clusters) and 13,810 exposed to standard care (6 clusters) during the outcome period (mITT analysis). Age, height, and weight were broadly similar between arms, but there were fewer women: of white ethnicity (56.2% versus 62.7%), and in the least deprived quintile of the Index of Multiple Deprivation (7.5% versus 16.5%) in the intervention arm during the outcome period. Antenatal detection of SGA was 25.9% in the intervention and 27.7% in the standard care arm (adjusted difference 2.2%, 95% confidence interval (CI) -6.4% to 10.7%; p = 0.62). Findings were consistent in full ITT analysis. Fidelity and dose of GAP implementation were variable, while a high proportion (88.7%) of women were reached. Use of routinely collected data is both a strength (cost-efficient) and a limitation (occurrence of missing data); the modest number of clusters limits our ability to study small effect sizes.

Conclusions: In this study, we observed no effect of GAP on antenatal detection of SGA compared to standard care. Given variable implementation observed, future studies should incorporate standardised implementation outcomes such as those reported here to determine generalisability of our findings.

Trial Registration: This trial is registered with the ISRCTN registry, ISRCTN67698474.
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http://dx.doi.org/10.1371/journal.pmed.1004004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212153PMC
June 2022

Preparing for Disease X: Ensuring Vaccine Equity for Pregnant Women in Future Pandemics.

Front Med (Lausanne) 2022 30;9:893292. Epub 2022 May 30.

Bill & Melinda Gates Foundation, Seattle, WA, United States.

Disease X represents a yet unknown human pathogen which has potential to cause a serious international epidemic or pandemic. The COVID-19 pandemic has illustrated that despite being at increased risk of severe disease compared with the general population, pregnant women were left behind in the development and implementation of vaccination, resulting in conflicting communications and changing guidance about vaccine receipt in pregnancy. Based on the COVID-19 experience, the COVAX Maternal Immunization Working Group have identified three key factors and five broad focus topics for consideration when proactively planning for a disease X pandemic, including 10 criteria for evaluating pandemic vaccines for potential use in pregnant women. Prior to any disease X pandemic, collaboration and coordination are needed to close the pregnancy data gap which is currently a barrier to gender equity in health innovation, which will aid in allowing timely access to life-saving interventions including vaccines for pregnant women and their infants.
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http://dx.doi.org/10.3389/fmed.2022.893292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9195576PMC
May 2022

Timing of Delivery for Twins With Growth Discordance and Growth Restriction: An Individual Participant Data Meta-analysis.

Obstet Gynecol 2022 06 2;139(6):1155-1167. Epub 2022 May 2.

Flinders Medical Centre, Adelaide, South Australia, and the Department of Obstetrics and Gynecology, Monash University, Clayton, Victoria, Australia; the Department of Obstetrics, Amsterdam Reproduction and Development Research Institute, Amsterdam UMC, University of Amsterdam, Amsterdam, the Julius Center for Health Sciences and Primary Care & Cochrane Netherlands, University Medical Center Utrecht, Utrecht University, Utrecht, the Department of Gynaecology and Obstetrics, GROW School of Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Department of Obstetrics and Gynecology, Haga Hospital, The Hague, the Department of Obstetrics and Gynecology, Gelre Hospitals Apeldoorn, Apeldoorn, and the Department of Obstetrics and Gynaecology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Atrium Health, Charlotte, North Carolina; the Maternal Fetal Medicine Unit, Department of Obstetrics, Vall d'Hebron Barcelona Hospital Campus, Universitat Autònoma de Barcelona, Barcelona, Spain; the Department of Obstetrics and Gynecology, Hospital das Clinicas, University of São Paulo, São Paulo, Brazil; the Department of Obstetrics and Gynecology, Sheba Medical Center, Tel-Hashomer, Sackler School of Medicine, Tel Aviv University, Tel Aviv, and the Department of Obstetrics and Gynecology, Samson Assuta Ashdod University Hospital, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel; the Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, the Departments of Obstetrics and Gynecology, Medicine, Community Health Sciences, and Pediatrics, and Alberta Children's Hospital Research Institute, University of Calgary, Calgary, Alberta, and the Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada; the Department of Obstetrics and Gynecology, ASST-Spedali Civili, and the Department of Clinical and Experimental Sciences, University of Brescia, Brescia, and the Fetal Therapy Unit "Umberto Nicolini" and the Department of Women, Mother and Newborn, Vittore Buzzi Children's Hospital, University of Milan, Milan, Italy; the Department of Maternal Fetal Medicine, Osaka Women's and Children's Hospital, Osaka, Japan; the Department of Fetal Medicine, The Aga Khan University, Karachi, Pakistan; the Department of Obstetrics and Gynecology, University Hospitals of Leuven, Leuven, Belgium; the Department of Obstetrics and Gynecology, American University of Beirut Medical Center, Beirut, Lebanon; the Departments of Clinical Biochemistry and Obstetrics, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; the Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Rockville, Maryland; the Mednax Center for Research, Education, Quality, and Safety, Sunrise, Florida; the Obstetrix Medical Group, Campbell, California; Unidad de Medicina Materno-Fetal, Instituto Valenciano de Infertilidad, Departamento de Pediatría, Obstetricia y Ginecología, and Servicio de Obstetricia, Hospital Universitario y Politécnico La Fe, Departamento de Pediatría, Obstetricia y Ginecología, Universidad de Valencia, Valencia, Spain; and the Fetal Medicine Unit, St George's Hospital, the Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, and the Twins Trust Centre for Research and Clinical Excellence, London, the Institute of Applied Health Research, University of Birmingham, Birmingham, and the Aberdeen Centre for Women's Health Research, University of Aberdeen, Aberdeen, United Kingdom.

Objective: First, to evaluate the risks of stillbirth and neonatal death by gestational age in twin pregnancies with different levels of growth discordance and in relation to small for gestational age (SGA), and on this basis to establish optimal gestational ages for delivery. Second, to compare these optimal gestational ages with previously established optimal delivery timing for twin pregnancies not complicated by fetal growth restriction, which, in a previous individual patient meta-analysis, was calculated at 37 0/7 weeks of gestation for dichorionic pregnancies and 36 0/7 weeks for monochorionic pregnancies.

Data Sources: A search of MEDLINE, EMBASE, ClinicalTrials.gov, and Ovid between 2015 and 2018 was performed of cohort studies reporting risks of stillbirth and neonatal death in twin pregnancies from 32 to 41 weeks of gestation. Studies from a previous meta-analysis using a similar search strategy (from inception to 2015) were combined. Women with monoamniotic twin pregnancies were excluded.

Methods Of Study Selection: Overall, of 57 eligible studies, 20 cohort studies that contributed original data reporting on 7,474 dichorionic and 2,281 monochorionic twin pairs.

Tabulation, Integration, And Results: We performed an individual participant data meta-analysis to calculate the risk of perinatal death (risk difference between prospective stillbirth and neonatal death) per gestational week. Analyses were stratified by chorionicity, levels of growth discordance, and presence of SGA in one or both twins. For both dichorionic and monochorionic twins, the absolute risks of stillbirth and neonatal death were higher when one or both twins were SGA and increased with greater levels of growth discordance. Regardless of level of growth discordance and birth weight, perinatal risk balanced between 36 0/7-6/7 and 37 0/7-6/7 weeks of gestation in both dichorionic and monochorionic twin pregnancies, with likely higher risk of stillbirth than neonatal death from 37 0/7-6/7 weeks onward.

Conclusion: Growth discordance or SGA is associated with higher absolute risks of stillbirth and neonatal death. However, balancing these two risks, we did not find evidence that the optimal timing of delivery is changed by the presence of growth disorders alone.

Systematic Review Registration: PROSPERO, CRD42018090866.
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http://dx.doi.org/10.1097/AOG.0000000000004789DOI Listing
June 2022

Cerebroplacental Ratio Prediction of Intrapartum Fetal Compromise according to the Interval to Delivery.

Fetal Diagn Ther 2022 7;49(4):196-205. Epub 2022 Jun 7.

Servicio de Obstetricia y Ginecología, Hospital Universitario y Politécnico La Fe, Valencia, Spain.

Introduction: A controversy exists about the accuracy of the cerebroplacental ratio (CPR) for the prediction of cesarean section for intrapartum fetal compromise (CS-IFC). Our aim was to evaluate whether the interval to delivery modifies the accuracy of CPR either as a single marker or combined with estimated fetal weight centile (EFWc), type of labor onset (TLO), and other clinical variables.

Methods: This was a multicenter retrospective study of 5,193 women with singleton pregnancies who underwent an ultrasound scan at 35+0-41+0 weeks and gave birth within 1 month of examination, at any of the participating hospitals in Spain, UK, and Italy. CS-IFC was diagnosed in case of an abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH <7.20, requiring urgent cesarean section. The diagnostic ability of CPR in multiples of the median (CPR MoM) was evaluated at different intervals to delivery, alone and combined with EFWc, TLO, and other pregnancy data such as maternal age, maternal body mass index, parity, and fetal sex, for the prediction of CS-IFC by means of ROC curves and logistic regression analysis.

Results: The predictive ability of CPR MoM for CS-IFC worsened with the interval to delivery. In general, the best prediction was obtained prior to labor and by adding information related to EFWc and TLO (AUC 0.71 [95% CI: 0.64-0.79], 0.73 [95% CI: 0.66-0.80], and 0.75 [95% CI: 0.69-0.81]; p < 0.0001). Addition of more clinical data did not improve prediction. In addition, results did not vary when only cases with spontaneous onset of labor were studied.

Conclusion: CPR MoM prediction of CS-IFC at the end of pregnancy worsens with the interval to delivery. Accordingly, it should be done in the short term and considering EFWc and TLO.
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http://dx.doi.org/10.1159/000525162DOI Listing
July 2022

Practice patterns amongst fetal centers performing intrauterine transfusions (PACT): An international survey study.

Eur J Obstet Gynecol Reprod Biol 2022 Jul 30;274:171-174. Epub 2022 May 30.

Department of Obstetrics and Gynecology, Baylor College of Medicine and Texas Children's Fetal Center, Houston, TX, USA.

Objectives: Fetal anemia secondary to incompatibility between maternal-fetal blood types can result in hydrops and demise. Intrauterine transfusions have improved survival in experience centers. Our objective was to determine the practice patterns amongst fetal centers.

Study Design: Thirteen fetal centers across the world were surveyed. Results from all participating centers were recorded, analyzed, and presented as ratios. Questions on the survey were related to experience of the physician, preferred methods of transfusion, fetal surveillance, and timing of delivery.

Results: Differences amongst centers were as follows: 54% of the centers performed transfusions in operating room, the remaining did them in a clinic room or close to the operating room; 31% did not use maternal anesthesia, 31% used oral or intravenous sedation and 38% used a combination of local with oral or intravenous sedation. The similarities include: 84% performed intravenous transfusions, while 2 centers reported intraperitoneal and intracardiac transfusions were performed for very early cases; 85% of centers performed the last transfusion at 34-35 weeks and 77% electively delivered their patients at 37 weeks.

Conclusion: Method of transfusion and delivery timing was similar in most centers; however, differences were seen in location of procedure, anesthetic coverage, and surveillance. Further assessment is needed to determine if these differences in practice have any potential neonatal effects.
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http://dx.doi.org/10.1016/j.ejogrb.2022.05.027DOI Listing
July 2022

Adverse pregnancy outcomes: biological essentialism versus embodied biology - Authors' reply.

Lancet 2022 05;399(10340):2014

Department of Health Services Research, London School of Hygiene & Tropical Medicine, London, UK.

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http://dx.doi.org/10.1016/S0140-6736(22)00171-4DOI Listing
May 2022

Antioxidants in Pregnancy: Do We Really Need More Trials?

Antioxidants (Basel) 2022 Apr 22;11(5). Epub 2022 Apr 22.

Systems Medicine, School of Medicine, University of Dundee, Dundee DD1 9SY, UK.

Human pregnancy can be affected by numerous pathologies, from those which are mild and reversible to others which are life-threatening. Among these, gestational diabetes mellitus and hypertensive disorders of pregnancy with subsequent consequences stand out. Health problems experienced by women during pregnancy and postpartum are associated with significant costs to health systems worldwide and contribute largely to maternal mortality and morbidity. Major risk factors for mothers include obesity, advanced maternal age, cardiovascular dysfunction, and endothelial damage; in these scenarios, oxidative stress plays a major role. Markers of oxidative stress can be measured in patients with preeclampsia, foetal growth restriction, and gestational diabetes mellitus, even before their clinical onset. In consequence, antioxidant supplements have been proposed as a possible therapy; however, results derived from large scale randomised clinical trials have been disappointing as no positive effects were demonstrated. This review focuses on the latest evidence on oxidative stress in pregnancy complications, their early diagnosis, and possible therapies to prevent or treat these pathologies.
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http://dx.doi.org/10.3390/antiox11050812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9137466PMC
April 2022

Single extracellular vesicle analysis in human amniotic fluid shows evidence of phenotype alterations in preeclampsia.

J Extracell Vesicles 2022 05;11(5):e12217

Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.

Amniotic fluid surrounding the developing fetus is a complex biological fluid rich in metabolically active bio-factors. The presence of extracellular vesicles (EVs) in amniotic fluid has been mainly related to foetal urine. We here characterized EVs from term amniotic fluid in terms of surface marker expression using different orthogonal techniques. EVs appeared to be a heterogeneous population expressing markers of renal, placental, epithelial and stem cells. Moreover, we compared amniotic fluid EVs from normal pregnancies with those of preeclampsia, a hypertensive disorder affecting up to 8% of pregnancies worldwide. An increase of CD105 (endoglin) expressing EVs was observed in preeclamptic amniotic fluid by bead-based cytofluorimetric analysis, and further confirmed using a chip-based analysis. HLA-G, a typical placental marker, was not co-expressed by the majority of CD105 EVs, in analogy with amniotic fluid stromal cell derived-EVs. At a functional level, preeclampsia-derived EVs, but not normal pregnancy EVs, showed an antiangiogenic effect, possibly due to the decoy effect of endoglin. Our results provide a characterization of term amniotic fluid-EVs, supporting their origin from foetal and placental cells. In preeclampsia, the observed antiangiogenic characteristics of amniotic fluid-EVs may reflect the hypoxic and antiangiogenic microenvironment and could possibly impact on the developing fetus or on the surrounding foetal membranes.
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http://dx.doi.org/10.1002/jev2.12217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115584PMC
May 2022

COVID-19 vaccination in pregnancy.

Am J Obstet Gynecol 2022 08 11;227(2):136-147. Epub 2022 May 11.

Fetal Medicine Unit, St George's Hospital, St George's University of London, London, England, United Kingdom; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University Hospitals NHS Foundation Trust, St George's University of London, London, England, United Kingdom; Liverpool Women's Hospital, Liverpool, United Kingdom. Electronic address:

Despite a recent endorsement from official and professional bodies unequivocally recommending COVID-19 vaccination, vaccine hesitancy among pregnant people remains high. The accumulated evidence demonstrates that pregnant people are a special risk group for COVID-19, with an increased risk of intensive care unit admission, extracorporeal membranous oxygenation requirement, preterm birth, and perinatal death. These risks are further increased with some variants of concern, and vaccination of pregnant people reduces the COVID-19-related increase in maternal or fetal morbidity. Data from more than 180,000 vaccinated persons show that immunization against COVID-19 with an mRNA vaccine is safe for pregnant people. Many observational studies comparing perinatal outcomes between vaccinated and unvaccinated pregnant people have had reassuring findings and did not demonstrate harmful effects on pregnancy or the newborn. Immunization with mRNA vaccines does not increase the risk of miscarriage, preterm delivery, low birthweight, maternal or neonatal intensive care unit admission, fetal death, fetal abnormality, or pulmonary embolism. Moreover, observational data corroborate the findings of randomized trials that mRNA vaccination is highly effective at preventing severe SARS-CoV-2 infection in pregnant people, emphasizing that the potential maternal and fetal benefits of vaccination greatly outweigh the potential risks of vaccination. Ensuring pregnant people have unrestricted access to COVID-19 vaccination should be a priority in every country worldwide.
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http://dx.doi.org/10.1016/j.ajog.2022.05.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9093065PMC
August 2022

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.

Nat Commun 2022 05 10;13(1):2414. Epub 2022 May 10.

Fetal Medicine Unit, St George's Hospital, St George's University of London, London, UK.

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.
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http://dx.doi.org/10.1038/s41467-022-30052-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9090726PMC
May 2022

Systematic review and critical evaluation of quality of clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy.

Am J Obstet Gynecol MFM 2022 May 2;4(5):100654. Epub 2022 May 2.

Center for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy (Dr. Di Girolamo, Dr. Capannolo, Dr. Buca, Prof. Liberati, and Prof. D'Antonio). Electronic address:

Objective: To systematically identify and critically assess the quality of clinical practice guidelines for the management of SARS-CoV-2 infection in pregnancy.

Data Sources: Medline, Scopus, and ISI Web of Science databases were searched until February 15, 2022.

Study Eligibility Criteria: Inclusion criteria were clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy. The risk of bias and quality assessments of the included clinical practice guidelines were performed using the Appraisal of Guidelines for REsearch and Evaluation II tool, which is considered the gold standard for quality assessment of clinical practice guidelines. To define a clinical practice guideline as of good quality, we adopted the cutoff score proposed by Amer et al: if the overall clinical practice guideline score was >60%, it was recommended.

Methods: The following clinical points related to the management of pregnant women with SARS-CoV-2 infection were addressed: criteria for maternal hospitalization, recommendations for follow-up fetal growth scan, specific recommendations against invasive procedures, management of labor, timing of delivery, postpartum care, and vaccination strategy.

Results: A total of 28 clinical practice guidelines were included. All recommended hospitalization only for severe disease; 46.1% (6/13) suggested a fetal growth scan after SARS-CoV-2 infection, whereas 23.1% (3/13) did not support this practice. Thromboprophylaxis with low-molecular-weight heparin was recommended in symptomatic women by 77.1% (7/9) of the clinical practice guidelines. None of the guidelines recommended administering corticosteroids only for the presence of SARS-CoV-2 infection in preterm gestation, unless specific obstetrical indication exists. Elective induction of labor from 39 weeks of gestation was suggested by 18.1% (2/11) of the clinical practice guidelines included in the present review, whereas 45.4% (5/11) did not recommend elective induction unless other obstetrical indications coexisted. There were 27% (3/11) of clinical practice guidelines that suggested shortening of the second stage of labor, and active pushing was supported by 18.1% (2/11). There was general agreement among the clinical practice guidelines in not recommending cesarean delivery only for the presence of maternal infection and in recommending vaccine boosters at least 6 months after the primary series of vaccination. The Appraisal of Guidelines for REsearch and Evaluation II standardized domain scores for the first overall assessment of clinical practice guidelines had a mean of 50% (standard deviation±21.82%), and 9 clinical practice guidelines scored >60%.

Conclusion: A significant heterogeneity was found in some of the main aspects of the management of SARS-CoV-2 infection in pregnancy, as reported by the published clinical practice guidelines.
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http://dx.doi.org/10.1016/j.ajogmf.2022.100654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9057927PMC
May 2022

The effect of the delta SARS-CoV-2 variant on maternal infection and pregnancy.

iScience 2022 May 25;25(5):104295. Epub 2022 Apr 25.

Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.

A greater proportion of pregnant women with COVID-19 have mild disease compared with their non-pregnant counterparts. Paradoxically, however, they are at higher risk of developing severe disease, requiring respiratory support and admission to intensive care. The delta SARS-Cov-2 variant is associated with increased risk of hospitalization and morbidity in unvaccinated pregnant populations. However, it is not known whether the worse pregnancy outcomes associated with the delta variant are due to a direct effect of the virus on the pregnancy, or whether this effect is mediated through more severe maternal infection. Here, we synthesize studies of COVID-19 pregnancies, focusing on the different routes of SARS-CoV-2 infection of lung and placenta, and the mechanisms of syncytial formation for each SARS-CoV-2 variant. To delineate COVID-19 complications in pregnant women, future studies should explore whether the delta variant causes greater placental infection compared to other variants and contributes to increased syncytial formation.
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http://dx.doi.org/10.1016/j.isci.2022.104295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9040522PMC
May 2022

Methodological Quality of Fetal Brain Structure Charts for Screening Examination and Targeted Neurosonography: A Systematic Review.

Fetal Diagn Ther 2022 22;49(4):145-158. Epub 2022 Apr 22.

Department of Obstetrics and Gynecology, Center for Fetal Care and High-Risk Pregnancy, University of Chieti, Chieti, Italy.

Introduction: Several fetal brain charts have been published in the literature and are commonly used in the daily clinical practice. However, the methodological quality of these charts has not been critically appraised.

Material And Methods: MEDLINE, EMBASE, CINAHL, and the Web of Science databases were searched electronically up to December 31, 2020. The primary outcome was to evaluate the methodology of the studies assessing the growth of fetal brain structures throughout gestation. A list of 28 methodological quality criteria divided into three domains according to "study design," "statistical and reporting methods," and "specific relevant neurosonography aspects" was developed in order to assess the methodological appropriateness of the included studies. The overall quality score was defined as the sum of low risk of bias marks, with the range of possible scores being 0-28. This quality assessment was applied to each individual study reporting reference ranges for fetal brain structures. Furthermore, we performed a subgroup analysis according to the different brain structures (ventricular and periventricular, fore-brain and midbrain cerebral and posterior fossa).

Results: Sixty studies were included in the systematic review. The overall mean quality score of the studies included in this review was 51.3%. When focusing on each of the assessed domains, the mean quality score was 53.7% for "study design," 54.2% for "statistical and reporting methods," and 38.6% for "specific relevant neurosonography aspects." The sample size calculation, the correlation with a postnatal imaging evaluation, and the whole fetal brain assessment were the items at the highest risk of bias for each domain assessed, respectively. The subgroup analysis according to different anatomical location showed the lowest quality score for ventricular and periventricular structures and the highest for cortical structures.

Conclusions: Most previously published studies reporting fetal brain charts suffer from poor methodology and are at high risk of biases, mostly when focusing on neurosonography issues. Further prospective longitudinal studies aiming at constructing specific growth charts for fetal brain structures should follow rigorous methodology to minimize the risk of biases, guarantee higher levels of reproducibility, and improve the standard of care.
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http://dx.doi.org/10.1159/000521421DOI Listing
July 2022

First-trimester prediction of uterine rupture in cesarean scar pregnancy.

Am J Obstet Gynecol 2022 08 20;227(2):353-355. Epub 2022 Apr 20.

Department of Obstetrics and Gynaecology, Centre for Fetal Care and High-Risk Pregnancy, University of Chieti, Chieti, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.ajog.2022.04.026DOI Listing
August 2022

First trimester examination of fetal anatomy: clinical practice guideline by the World Association of Perinatal Medicine (WAPM) and the Perinatal Medicine Foundation (PMF).

J Perinat Med 2022 Apr 25. Epub 2022 Apr 25.

Department of Obstetrics and Gynecology, Medical Faculty, Skopje University, Skopje, North Macedonia.

This recommendation document follows the mission of the World Association of Perinatal Medicine in collaboration with the Perinatal Medicine Foundation. We aim to bring together groups and individuals throughout the world for precise standardization to implement the ultrasound evaluation of the fetus in the first trimester of pregnancy and improve the early detection of anomalies and the clinical management of the pregnancy. The aim is to present a document that includes statements and recommendations on the standard evaluation of the fetal anatomy in the first trimester, based on quality evidence in the peer-reviewed literature as well as the experience of perinatal experts around the world.
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http://dx.doi.org/10.1515/jpm-2022-0125DOI Listing
April 2022

Use of induction of labour and emergency caesarean section and perinatal outcomes in English maternity services: a national hospital-level study.

BJOG 2022 Apr 21. Epub 2022 Apr 21.

Department of Health Services Research and Policy, , London School of Hygiene and Tropical Medicine, 15-17 Tavistock Place, London WC1H 9SH, UK.

Objectives: To assess the association between hospital-level rates of induction of labour and emergency caesarean section, as measures of "practice style", and rates of adverse perinatal outcomes.

Design: National study using electronic maternity records.

Setting: English National Health Service.

Participants: Hospitals providing maternity care to women between April 2015 and March 2017.

Main Outcome Measures: Stillbirth, admission to a neonatal unit, and babies receiving mechanical ventilation.

Results: Among singleton term births, the risk of stillbirth was 0.15%; of admission to a neonatal unit 5.4%; and of mechanical ventilation 0.54%. There was considerable between-hospital variation in the induction of labour rate (minimum 17.5%, maximum 40.7%) and the emergency caesarean section rate (minimum 5.6%, maximum 17.1%). Women who gave birth in hospitals with a higher induction of labour rate had better perinatal outcomes. For each 5%-point increase in induction, there was a decrease in the risk of term stillbirth by 9% (OR 0.91; 95% CI 0.85 to 0.97) and mechanical ventilation by 14% (OR 0.86; 95% CI 0.79 to 0.94). There was no significant association between hospital-level induction of labour rates and neonatal unit admission at term (p>0.05). There was no significant association between hospital-level emergency caesarean section rates and adverse perinatal outcomes (p always >0.05).

Conclusions: There is considerable between-hospital variation in the use of induction of labour and emergency caesarean section. Hospitals with a higher induction rate had a lower risk of adverse birth outcomes. A similar association was not found for caesarean section.
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http://dx.doi.org/10.1111/1471-0528.17193DOI Listing
April 2022

Assessment of pericallosal artery at 11-14 weeks of gestation: Cohort study and meta-analysis.

J Clin Ultrasound 2022 Mar 22. Epub 2022 Mar 22.

Centre for High-Risk Pregnancy and Fetal Care, Department of Obstetrics and Gynaecology, University of Chieti, Chieti, Italy.

Objectives: To report the rate of visualization of the pericallosal artery (PCA) in the first trimester of pregnancy (11-14 weeks).

Methods: Prospective observational study of consecutive fetuses undergoing first trimester risk assessment for chromosomal anomalies. The presence of PCA was assessed in a midsagittal view of fetal brain using high-definition power Color Doppler. A normal course of the PCA was defined as the visualization of an artery emerging from the anterior cerebral artery running parallel the corpus callosum (CC). The reference standard was the visualization of CC and PCA between the 20 and 22 weeks of gestation. We also performed a systematic review and meta-analysis of the published literature. Multivariate logistic regression and random-effect meta-analyses of proportion were used to analyze the data.

Results: Cohort study: Five-hundred women were included. PCA was identified trans-abdominally or transvaginally at 11-14 weeks of gestation in 98.8% (95% CI 97.4-99.6: 494/500); of the four cases of PCA not identified one had a diagnosis of complete agenesis of the corpus callosum during the anomaly scan which was confirmed at birth. Systematic review of the published literature: Six studies (1093 fetuses, including the present series) were included. The PCA was detected at the 11-14 weeks scan and confirmed to co-exist with a normal CC at time of the anomaly scan in 96.9% (95% CI 93.8-99.0); 20.6% (95% CI 5.7-41.7) of fetuses with no clear identification of the PCA at the 11-14 weeks scan had a normal appearance of the CC at the time of anomaly scan.

Conclusion: Prenatal ultrasonography has a high diagnostic accuracy in detecting PCA in the first trimester. Visualization of the PCA at the time of 11-14 scan is highly specific for the presence of a normal CC later in pregnancy.
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http://dx.doi.org/10.1002/jcu.23191DOI Listing
March 2022

Atypical twin-to-twin transfusion syndrome.

Ultrasound Obstet Gynecol 2022 Mar 19. Epub 2022 Mar 19.

Fetal Medicine and Surgery Center, Medicina Fetal Mexico, Quer ́etaro, Mexico.

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http://dx.doi.org/10.1002/uog.24899DOI Listing
March 2022

SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis.

BMJ 2022 03 16;376:e067696. Epub 2022 Mar 16.

UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland.

Objectives: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring.

Design: Living systematic review and meta-analysis.

Data Sources: Major databases between 1 December 2019 and 3 August 2021.

Study Selection: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies.

Data Extraction: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal).

Results: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean.

Conclusion: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring.

Systematic Review Registration: PROSPERO CRD42020178076.

Readers' Note: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.
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http://dx.doi.org/10.1136/bmj-2021-067696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8924705PMC
March 2022

Placenta accreta spectrum disorders in twin pregnancies as an under reported clinical entity: a case series and systematic review.

J Matern Fetal Neonatal Med 2022 Mar 13:1-4. Epub 2022 Mar 13.

Centre for Fetal Care and High-Risk Pregnancy, Department of Obstetrics and Gynecology, University of Chieti, Chieti, Italy.

Recent reports suggested a potential association between twin pregnancy and the occurrence of placenta accreta spectrum (PAS) disorders. Despite this, scarce data on PAS disorders in twins has been reported in the published literature. We present a series of twelve twin pregnancies complicated by PAS from two large institutions over 5 years. A systematic review of the literature was also conducted in order to find studies reporting on the risk factors, prenatal diagnosis using ultrasound and clinical outcomes of PAS in twin pregnancies.
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http://dx.doi.org/10.1080/14767058.2021.2005568DOI Listing
March 2022

Myo-inositol nutritional supplement for prevention of gestational diabetes (EMmY): a randomised, placebo-controlled, double-blind pilot trial with nested qualitative study.

BMJ Open 2022 03 11;12(3):e050110. Epub 2022 Mar 11.

WHO Collaborating Centre for Global Women's Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

Objectives: To determine the feasibility and acceptability of conducting a randomised trial on the effects of myo-inositol in preventing gestational diabetes in high-risk pregnant women.

Design: A multicentre, double-blind, placebo-controlled, pilot randomised trial with nested qualitative evaluation.

Setting: Five inner city UK National Health Service hospitals PARTICIPANTS: Multiethnic pregnant women at 12 and 15 weeks' gestation with risk factors for gestational diabetes.

Interventions: 2 g of myo-inositol or placebo, both included 200 µg folic acid, twice daily until delivery.

Primary Outcome Measures: Rates of recruitment, randomisation, adherence and follow-up.

Secondary Outcome Measures: Glycaemic indices (including homoeostatic model assessment-insulin resistance HOMA-IR), gestational diabetes (diagnosed using oral glucose tolerance test at 28 weeks and by delivery), maternal, perinatal outcomes, acceptability of intervention and costs.

Results: Of the 1326 women screened, 58% (773/1326) were potentially eligible, and 27% (205/773) were recruited. We randomised 97% (198/205) of all recruited women (99 each in intervention and placebo arms) and ascertained outcomes in 90% of women (178/198) by delivery. The mean adherence was 52% (SD 44) at 28 weeks' and 34% (SD 41) at 36 weeks' gestation. HOMA-IR and serum insulin levels were lower in the myo-inositol vs placebo arm (mean difference -0.6, 95% CI -1.2 to 0.0 and -2.69, 95% CI -5.26 to -0.18, respectively). The study procedures were acceptable to women and healthcare professionals. Women who perceived themselves at high risk of gestational diabetes were more likely to participate and adhere to the intervention. The powder form of myo-inositol and placebo, along with nausea in pregnancy were key barriers to adherence.

Conclusions: A future trial on myo-inositol versus placebo to prevent gestational diabetes is feasible. The intervention will need to be delivered in a non-powder form to improve adherence. There is a signal for efficacy in reducing insulin resistance in pregnancy with myo-inositol.

Trial Registration Number: ISRCTN48872100.
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http://dx.doi.org/10.1136/bmjopen-2021-050110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919454PMC
March 2022

Diagnosis and Monitoring of White Coat Hypertension in Pregnancy: an ISSHP Consensus Delphi Procedure.

Hypertension 2022 05 10;79(5):993-1005. Epub 2022 Mar 10.

Fetal Medicine Unit, St George's Hospital (A.K.), St George's University of London, United Kingdom.

Background: There is no accepted definition or standardized monitoring for white coat hypertension in pregnancy. This Delphi procedure aimed to reach consensus on out-of-office blood pressure (BP) monitoring, and white coat hypertension diagnostic criteria and monitoring.

Method: Relevant international experts completed three rounds of a modified Delphi questionnaire. For each item, the predefined cutoff for group consensus was ≥70% agreement, with 60% to 70% considered to warrant reconsideration at the subsequent round, and <60% considered insufficient to warrant consideration.

Results: Of 230 experts, 137 completed the first round and 114 (114/137, 83.2%) completed all three. For out-of-office BP monitoring, there was consensus that home BP monitoring (HBPM) should be chosen; instructions given, pairs of BP values taken, opportunity given for women to qualify values they do not regard as valid, and BP considered evaluated when ≥25% of values are above a cutoff. For HBPM, BP should be taken at least 2 to 3 d/wk, at minimum in the morning; however, many factors may affect frequency and timing. Experts endorsed a clinic BP <140/90 mm Hg as normal. While not reaching consensus, most agreed that HBPM values should be lower than clinic BP. Among those, HBPM <135/85 mm Hg was considered normal. There was consensus that white coat hypertension warrants: HBPM at least 1 d/wk before 20 weeks, 2 to 3 d/wk after 20 weeks or if persistent hypertension develops, and symptom monitoring (ie, headache, visual symptoms, and right upper quadrant/epigastric pain).

Conclusions: Consensus-based diagnostic criteria and monitoring strategies should inform clinical care and research, to facilitate evaluation of out-of-office BP monitoring on pregnancy outcomes.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18356DOI Listing
May 2022

Role of balloon tamponade during cesarean section in women with placenta previa: a systematic review and meta-analysis.

Minerva Obstet Gynecol 2022 Mar 2. Epub 2022 Mar 2.

Department of Obstetrics and Gynecology, Center for Fetal Care and High-Risk Pregnancy, University of Chieti, Chieti, Italy -

Introduction: To explore the role of balloon tamponade insertion in pregnancies complicated by placenta previa.

Evidence Acquisition: Medline, Embase and ClinicalTrials.gov databases were searched electronically on October 17. Inclusion criteria were women with placenta previa undergoing, compared to those not undergoing, balloon tamponade insertion at the time of the cesarean section (CS). The outcomes observed were total, intra- and post-operative estimated blood loss (EBL), need for blood transfusion, admission to intensive care unit (ICU), hysterectomy and additional surgical or medical procedures to achieve hemostasis. Results were reported as pooled odd ratios (OR) or mean difference (MD) according to the outcome investigated.

Evidence Synthesis: Four studies (593 women) were included. Total EBL was significantly lower in women undergoing balloon tamponade insertion during CS compared to controls (MD: -556.3, 95% CI -496 to -617.0, p=0.001). Likewise, women undergoing balloon tamponade insertion had significantly lower intra- (MD: -699.8, 95% CI -766.1 to -633.5, p=0.001) and post-operative (MD: -1162ml (95% CI -1211.1 to -1134.4, p<0.001) compared to women who did undergo such procedure. Furthermore, women undergoing balloon tamponade insertion had a significantly lower risk of requiring additional surgical (OR: 0.16, 95% CI 0.1-0.5, I2: 0%; p=0.001) or medical (OR: 0.02, 95% CI 0.003-0.1, I2: 0; p=0.001) procedures to achieve hemostasis. Conversely, there was no significant difference in either the need for blood transfusion (p= 0.071), admission to ICU (p= 0.459) or need for hysterectomy (p= 0.312) between women undergoing, compared to those not undergoing, balloon tamponade insertion during CS for placenta previa.

Conclusions: Elective balloon tamponade insertion at the time of CS for placenta previa seems to be associated with a lower EBL and a reduced risk of additional medical and surgical procedures to control hemostasis. Large and adequately powered randomized controlled trials are needed to validate these results and introduce elective balloon tamponade insertion at the time of CS for placenta previa in clinical practice.
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http://dx.doi.org/10.23736/S2724-606X.22.05055-2DOI Listing
March 2022

COVID-19 booster doses in pregnancy and global vaccine equity.

Lancet 2022 03 18;399(10328):907-908. Epub 2022 Feb 18.

Fetal Medicine Unit, St George's Hospital, St George's University of London, London SW17 0QT, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George's University of London, London SW17 0QT, UK. Electronic address:

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http://dx.doi.org/10.1016/S0140-6736(22)00166-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856664PMC
March 2022

Standardization in the definition and management of late fetal growth restriction is needed to optimize perinatal outcome.

Am J Obstet Gynecol MFM 2022 Feb 15:100597. Epub 2022 Feb 15.

Department of Obstetrics and Gynaecology, Fondazione Policlinico Tor Vergata, Università Roma Tor Vergata, Rome, Italy.

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http://dx.doi.org/10.1016/j.ajogmf.2022.100597DOI Listing
February 2022

Arterial stiffness throughout pregnancy: Arteriograph device-specific reference ranges based on a low-risk population.

J Hypertens 2022 05 14;40(5):870-877. Epub 2022 Feb 14.

Maternal and Fetal Medicine Unit, University Hospitals of Leicester NHS Trust, Leicester.

Objective: The maternal cardiovascular system undergoes significant adaptation during pregnancy. We aimed to examine the changes in arterial stiffness parameters during normal pregnancy and establish reference ranges for the general population.

Methods: We performed a prospective cross-sectional observational study at the University Hospitals of Leicester. We included low-risk healthy pregnant women with singleton and viable pregnancies with no evidence of foetal abnormality or aneuploidy. Smokers, women with pre-existing or gestational hypertensive disorders and diabetes, booking BMI at least 30, on medication that could affect cardiac function and/or those who delivered before 37 completed weeks of gestation, and/or a neonate with birthweight less than 10th centile were excluded. Brachial (BrAIx) and aortic augmentation indices (AoAIx), and pulse wave velocity (PWV) were assessed using the Arteriograph. Data were analysed using a linear mixed model.

Results: We analysed a total of 571 readings from 259 women across different gestational ages and present the 10th, 25th, 50th, 75th and 90th centiles for BrAIx, AoAIx and PWV from 12+0 to 42+0 weeks' gestation. All haemodynamic variables were significantly associated with maternal heart rate. BrAIx, AoAIx and PWV demonstrated significant change with gestation, with all reaching their lowest value in the second trimester.

Conclusion: The current study presents reference ranges for BrAIx, AoAIx and PWV in low-risk singleton pregnancies. Further work is required to establish if women in whom measures of arterial stiffness lie above the 90th centile could be at increased risk of adverse pregnancy outcomes and to identify the optimum time for screening.
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http://dx.doi.org/10.1097/HJH.0000000000003086DOI Listing
May 2022

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

Hypertension 2022 03 4;79(3):614-628. Epub 2022 Jan 4.

Department of Women and Children's Health, King's College London, United Kingdom (P.v.D., L.A.M.).

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 β-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.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8823910PMC
March 2022
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