COVID-19 in pregnant women: a systematic review and meta-analysis on the risk and prevalence of pregnancy loss

Human Reproduction Update, Год журнала: 2023, Номер 30(2), С. 133 - 152

Опубликована: Ноя. 28, 2023

Abstract BACKGROUND Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates be stillborn or admitted a neonatal unit. The World Health Organization declared in May 2023 an end the disease 2019 (COVID-19) pandemic as global health emergency. However, pregnant still becoming SARS-CoV-2 there is limited information available regarding effect of infection early pregnancy on outcomes. OBJECTIVE AND RATIONALE We conducted this systematic review determine prevalence loss SARS-Cov-2 compare risk without infection. SEARCH METHODS Our based prospectively registered protocol. search PregCov19 consortium was supplemented extra electronic specifically up 10 March PubMed, Google Scholar, LitCovid. included retrospective prospective studies infection, provided that they contained losses first and/or second trimester. Primary outcome miscarriage defined before 20 weeks gestation, however, reported 22 24 were also included. Additionally, we report occur at trimester specifying gestational age, for only when study presented stillbirths foetal separately from miscarriages. Data stratified into Secondary outcomes ectopic (any extra-uterine pregnancy), termination pregnancy. At least three researchers independently extracted data assessed quality. calculated odds ratios (OR) differences (RDs) corresponding 95% CI pooled using random effects meta-analysis. To estimate prevalence, performed meta-analysis proportions. Heterogeneity by I2. OUTCOMES 120 comprising total 168 444 infection; which 18 233 Evidence level considered low moderate certainty, mostly owing selection bias. did not find evidence association between (OR 1.10, 0.81–1.48; I2 = 0.0%; RD 0.0012, −0.0103 0.0127; 0%; 9 studies, 4439 women). Miscarriage occurred 9.9% (95% 6.2–14.0%; 68%; 46 1797 women) SARS CoV-2 1.2% 0.3–2.4%; 34%; 33 studies; 3159 proportion pregnancies 1.4% 0.02–4.2%; 66%; 14 950 Termination 0.6% 0.01–1.6%; 79%; 39 1166 WIDER IMPLICATIONS found no indication increases provide better estimates, well-designed needed include conception consider clinical manifestation severity loss, well potential confounding factors such previous loss. For practice, should advised take precautions avoid exposure receive vaccination.

Язык: Английский

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Transmission of SARS-CoV-2 from mother to fetus or neonate: What to know and what to do?

Seminars in Fetal and Neonatal Medicine, Год журнала: 2023, Номер 28(1), С. 101429 - 101429

Опубликована: Фев. 1, 2023

Язык: Английский

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Covid-19 infection and vaccination during first trimester and risk of congenital anomalies: Nordic registry based study

BMJ, Год журнала: 2024, Номер unknown, С. e079364 - e079364

Опубликована: Июль 17, 2024

To evaluate the risk of major congenital anomalies according to infection with or vaccination against covid-19 during first trimester pregnancy. Prospective Nordic registry based study. Sweden, Denmark, and Norway. 343 066 liveborn singleton infants in Norway, an estimated start pregnancy between 1 March 2020 14 February 2022, identified using national health registries. Major were categorised EUROCAT (European Surveillance Congenital Anomalies) definitions. The after was assessed by logistic regression, adjusting for maternal age, parity, education, income, country origin, smoking, body mass index, chronic conditions, date 17 704 (5.2%) had a anomaly. When evaluating associated trimester, adjusted odds ratio ranged from 0.84 (95% confidence interval 0.51 1.40) eye 1.12 (0.68 1.84) oro-facial clefts. Similarly, (0.31 2.31) nervous system 1.69 (0.76 3.78) abdominal wall defects. Estimates 10 11 subgroups less than 1.04, indicating no notable increased risk. Covid-19 not anomalies.

Язык: Английский

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Stillbirth: we can do better

American Journal of Obstetrics and Gynecology, Год журнала: 2024, Номер 231(2), С. 152 - 165

Опубликована: Май 23, 2024

Язык: Английский

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Diagnostic evaluation to identify infection-attributable stillbirth

Journal of Perinatology, Год журнала: 2025, Номер unknown

Опубликована: Март 6, 2025

To characterize stillbirth evaluations, including the frequency and yield of investigations for infections causing stillbirth. Retrospective cohort stillbirths at three university-affiliated perinatal centers from 2017 to 2022. The primary outcome was adherence American College Obstetrics Gynecology core evaluation recommendations (placental pathology, fetal autopsy, genetic testing). We further characterized prevalence specific testing evaluate infection-attributable etiologies. included 399 stillbirths. Placental pathology performed in 387 cases (97.0%), 163 (40.9%), autopsy 126 (31.6%). Fetal bacterial cultures were obtained 73 (18.2%) cases; potential pathogens isolated 21/73 (28.8%). Viral sent infrequently, with variable yield. Six had identified as probable Adherence poor, infection infrequent. Infection-attributable may be underestimated.

Язык: Английский

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COVID and Early Pregnancy

Early pregnancy, Год журнала: 2025, Номер unknown, С. 255 - 261

Опубликована: Апрель 16, 2025

Язык: Английский

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Single-nucleus transcriptional profiling of the placenta reveals the syncytiotrophoblast stress response to COVID-19

American Journal of Obstetrics and Gynecology, Год журнала: 2025, Номер 232(4), С. S160 - S175.e7

Опубликована: Апрель 1, 2025

COVID-19 in pregnancy is associated with placental immune activation, inflammation, and vascular malperfusion, but its impact on syncytiotrophoblast biology function unclear. This study aimed to determine the effects of maternal syncytiotrophoblasts using single-nucleus transcriptional profiling compare stress responses preeclampsia. For characterization syncytiotrophoblasts, we used RNA sequencing platform, single-cell combinatorial indexing (sci-RNA-seq3), profile villi fetal membranes from unvaccinated patients symptomatic at birth (n = 4), gestational age-matched controls a case critical second trimester delivery term 1). Clustering nuclei differential gene expression analysis was performed Seurat. Gene ontology conducted Enrichr. High-confidence target identify key transcription factor nodes governing response SARS-CoV-2 infection. Bioinformatic approaches were further dataset published preeclampsia signatures. Tissue analysis, including immunofluorescence, validate data histology for an expanded cohort placentas: 6), asymptomatic 3), 5), severe features 7). The analyzed comprised 15 cell clusters 47,889 nuclei. We identified 3 representing fusing mature overlapping distinct COVID-19. analyses indicated that following alterations syncytiotrophoblasts: (1) endoplasmic reticulum activation signaling pathways, unfolded protein integrated response; (2) regulation by CCAAT/enhancer-binding beta (CEBPB), master lineage; (3) upregulation preeclampsia-associated genes. Using complementary methods, confirmed increased levels proteins (eg, BiP, G3BP1) (spliced XBP1 mRNA), CEBPB (phosphorylation) Increased cytotrophoblast proliferation (Ki-67) also detected COVID-19, consistent trophoblast injury. Markers demonstrated similarities phenotype Maternal lineage factor, CEBPB. Similarities between provide insights into their clinical association.

Язык: Английский

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COVID-19 infection history as a risk factor for early pregnancy loss: results from the electronic health record-based Southeast Texas COVID and Pregnancy Cohort Study

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Май 9, 2025

The effects of SARS-CoV-2 infection before or during pregnancy on outcomes are still largely unknown. We hypothesized that COVID-19 in early is a risk factor for adverse outcomes, particularly miscarriage. examined the relationship between and including spontaneous abortion, ectopic pregnancy, preterm delivery large, retrospective, electronic health record (EHR)-based cohort, from 2019 to 2023. Generalized estimating equation modeling was performed identify factors outcomes. Study exposures included age, race/ethnicity, comorbidity burden, neighborhood-level social vulnerability. In Southeast Texas Pregnancy COVID Cohort (26,783 episodes), miscarriage among episodes with miscarriage, livebirth, outcome 6.3% (1514/ 24,119). multivariable modeling, history both mild moderate severe were associated (adjusted odds ratio (aOR) 2.48, confidence interval (CI) 2.21-2.78 aOR 2.81, CI 1.8-4.38, respectively). Additionally, same model, first trimester (aOR 2.31, 1.96-2.72 2.45, 1.12-5.35, prior identified as abortion this study sample. These findings highlight importance vaccination post-COVID management pregnant people those planning pregnancy.

Язык: Английский

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Stillbirths due to placental COVID infection associated with chronic histiocytic intervillositis do not recur in subsequent pregnancies

Journal of Infection, Год журнала: 2024, Номер 88(2), С. 215 - 217

Опубликована: Янв. 11, 2024

During the COVID-19 pandemic, when SARS-CoV-2 B1.617.2 (Delta) variant was dominant, infected pregnant women had a 4-fold increased risk of stillbirth compared with non-infected (2.70% vs. 0.63%).1DeSisto C.L. Wallace B. Simeone R.M. Polen K. Ko J.Y. Meaney-Delman D. et al.Risk for among and without at delivery hospitalization - United States, March 2020-September 2021.MMWR Morb Mortal Wkly Rep. 2021; 70: 1640-1645https://doi.org/10.15585/mmwr.mm7047e1Crossref PubMed Google Scholar The placenta in these stillbirths showed COVID placentitis, combination within syncytiotrophoblast triad histological features: chronic histiocytic intervillositis, trophoblast necrosis, massive perivillous fibrin deposition. placentitis only occurred minority who tested positive pregnancy (∼1.5%).2Colley C.S. Hutchinson J.C. Whitten S.M. Siassakos Sebire N.J. Hillman S.L. Routine placental histopathology findings from testing during pregnancy: Retrospective cohort comparative study.BJOG. 2023; 130: 959-967https://doi.org/10.1111/1471-0528.17476Crossref Scopus (3) Fetal deaths Delta wave usually days mild maternal infection, stillborn fetuses were appropriately-grown gestational age (AGA).3Alcover N. Regiroli G. Benachi A. Vauloup-Fellous C. Vivanti De Luca Systematic review synthesis late miscarriages following infections.Am J Obstet Gynecol. 229: 118-128https://doi.org/10.1016/j.ajog.2023.01.019Abstract Full Text PDF (6) Chronic intervillositis (CHI) has also been reported alongside other infections, including malaria, cytomegalovirus listeriosis.4Marchaudon V. Devisme L. Petit S. Ansart-Franquet H. Vaast P. Subtil unknown etiology: clinical features consecutive series 69 cases.Placenta. 2011; 32: 140-145https://doi.org/10.1016/j.placenta.2010.11.021Crossref (60) In cases, infiltration CD68+ histiocytes leads to obliteration intervillous space, preventing maternal-fetal exchange that is vital fetal growth survival. emerged as latest pathogen capable causing CHI. Its global scale thrown importance this finding its potential catastrophic consequences into sharp relief. CHI occurs absence resembles histologically, but distinct devastating disorder associated recurrent loss.5Labarrere Mullen E. Fibrinoid trophoblastic necrosis intervillositis: an extreme villitis etiology.Am Reprod Immunol Microbiol. 1987; 15: 85-91https://doi.org/10.1111/j.1600-0897.1987.tb00162.xCrossref (83) This form affects 1 2000 pregnancies diagnosed >5% space occupied by histiocytes, infection.6Sauvestre F. Mattuizzi Sentilhes Poingt M. Blanco Houssin al.Chronic Development grading scoring system strongly poor perinatal outcomes.Am Surg Pathol. 2020; 44: 1367-1373https://doi.org/10.1097/PAS.0000000000001549Crossref (7) It causes miscarriage, severe restriction, carries high recurrence (100% cases). etiology non-infectious poorly understood, similarity rejected solid organ allografts suggests immunological mechanism.7Cornish E.F. McDonnell T. Williams D.J. inflammatory disorders adverse outcome.Front Immunol. 2022; 13825075https://doi.org/10.3389/fimmu.2022.825075Crossref (21) On basis, over last 30 years, have treated subsequent variety immunosuppressive regimens. These tempered may improve outcomes.7Cornish Scholar, 8Brady C.A. Batra Church Tower Crocker I.P. al.Immunomodulatory therapy reduces severity lesions intervillositis.Front Med. 8753220https://doi.org/10.3389/fmed.2021.753220Crossref (14) uncertain whether (or infections) recurs same way (immune-CHI). important knowledge gap, it unclear previous due should be considered immunosuppression future pregnancy. aim study investigate hypothesis SARS-CoV-2-associated (COVID-CHI) does not recur. We identified our maternity services had: (1) or miscarriage histologically proven COVID-CHI; (2) completed histology available (primary cohort). Demographic, medical, obstetric outcome data collected. then approached larger group (validation cohort) designing online survey, which disseminated social media support forum. Only loss COVID-CHI (whatever outcome) eligible. survey anonymously, no patient-identifiable work approved relevant research ethics committees (London: 19/LO/0105; Leiden: B21.034; Paris: CEROG 2021-OBST-0503). All participants primary provided written informed consent publication. Five underwent institutions. five ended live birth infant Comparative shown Fig. 1. A further 14 resulting overall 19 women. total 21 pregnancies, 19/21 (90%) 16/21 (76%) available. Table compares outcomes index pregnancies.Table 1Maternal demographics, medication use, ending death (n = 19), followed one more 21). Birthweight centiles calculated using INTERGROWTH-21st birthweight centile calculator. P-values Mann-Whitney U test (given non-normal distribution data) GraphPad Prism.* Low-dose aspirin (LDA): 75-160 mg daily. Prophylactic low-molecular-weight heparin (LMWH): variable formulations, e.g. enoxaparin 40 once daily.† four patients hydroxychloroquine and/or prednisolone their received LDA prophylactic LMWH.‡ Two another pathology (non-CHI) detected placenta. One focal ischemia vascular malperfusion preeclampsia; distal villous immaturity large-for-gestational-age Open table new tab * † LMWH. ‡ results show despite similarities immune-CHI, are inflammation. rate 90% overall, 100% those progressed beyond 16 weeks' gestation. Immunosuppression appears unnecessary COVID-CHI, most went on normal immunomodulatory treatment. confirm earlier observation fetus affected AGA (median 35th cohort).3Alcover Although smaller than unaffected siblings, acute pathology, opposed restriction (recurrent) immune-CHI.4Marchaudon interesting speculate why proved pathogenic Alpha Omicron variants. Possible mechanisms include higher levels viremia enhanced cleavage S protein furin, serine protease highly expressed syncytiotrophoblast. Furin-mediated facilitates viral entry host cells via binding angiotensin-converting enzyme-2 (ACE2) receptor.9Takeda Proteolytic activation spike protein.Microbiol 66: 15-23https://doi.org/10.1111/1348-0421.12945Crossref (75) Since superseded Omicron, there known cases infection. However, continues circulate variants could lead Vaccination COVID-associated therefore remain strong recommendation all women, especially COVID-CHI.10Magnus M.C. Örtqvist A.K. Dahlqwist Ljung R. Skår Oakley al.Association vaccination outcomes.JAMA. 327: 1469-1477https://doi.org/10.1001/jama.2022.3271Crossref (85) several limitations: small numbers, self-reporting validation cohort, incomplete pregnancies. Quantifying dependent specimens being submitted analysis (irrespective examined expert pathologist. Given rarity patient described here particularly hard-to-reach group. experienced themselves motivated address uncertainties about implications diagnosis, demonstrated dedicated 180 members. Our provides reassurance can expect outcome. observations likely apply infections CHI, remains confirmed. Unlike inflammation required. Dr Emily Cornish supported MRC Clinical Research Training Fellowship (MR/V028731/1) funds investigation pathogenesis intervillositis. Sam Schoenmakers funding Strong Babies. Thomas MRF fellowship (MRF-057-0004-RG-MCDO-C0800). Professor David NIHR University College London Hospitals Biomedical Centre.

Язык: Английский

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Neonatal outcomes of maternal prenatal coronavirus infection

Pediatric Research, Год журнала: 2023, Номер 95(2), С. 445 - 455

Опубликована: Дек. 6, 2023

Язык: Английский

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