Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

BMJ 2020370 doi: https://doi.org/10.1136/bmj.m3320 (Published 01 September 2020)
Cite this as: BMJ 2020;370:m3320

  1. John Allotey, senior research fellow in epidemiology and women’s health12,
  2. Elena Stallings, researcher34,
  3. Mercedes Bonet, medical officer5,
  4. Magnus Yap, medical student6,
  5. Shaunak Chatterjee, medical student6,
  6. Tania Kew, medical student6,
  7. Luke Debenham, medical student6,
  8. Anna Clavé Llavall, medical student6,
  9. Anushka Dixit, medical student6,
  10. Dengyi Zhou, medical student6,
  11. Rishab Balaji, medical student6,
  12. Siang Ing Lee, researcher1,
  13. Xiu Qiu, chief consultant of women’s health789,
  14. Mingyang Yuan, researcher17,
  15. Dyuti Coomar, research fellow1,
  16. Madelon van Wely, clinical epidemiologist10,
  17. Elizabeth van Leeuwen, medical specialist11,
  18. Elena Kostova, managing editor10,
  19. Heinke Kunst, senior lecturer and consultant in respiratory medicine1213,
  20. Asma Khalil, professor of obstetrics and maternal-fetal medicine14,
  21. Simon Tiberi, infectious disease consultant1213,
  22. Vanessa Brizuela, doctor of public health5,
  23. Nathalie Broutet, medical officer5,
  24. Edna Kara, public health specialist3,
  25. Caron Rahn Kim, medical officer5,
  26. Anna Thorson, professor in global infectious disease epidemiology5,
  27. Olufemi T Oladapo, acting head of maternal and perinatal health unit5,
  28. Lynne Mofenson, paediatric infectious disease specialist15,
  29. Javier Zamora, senior lecturer in biostatistics3416,
  30. Shakila Thangaratinam, professor of maternal and perinatal health217,
  31. for PregCOV-19 Living Systematic Review Consortium

Author affiliations

  1. Correspondence to: S Thangaratinam s.thangaratinam.1@bham.ac.uk (or @thangaratinam on Twitter)
  • Accepted 23 August 2020

Abstract

Objective To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).

Design Living systematic review and meta-analysis.

Data sources Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists.

Study selection Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.

Data extraction At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.

Results 77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I2=74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I2=0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I2=0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19.

Conclusion Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease.

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.

Disproportionate impact of COVID-19 among pregnant and postpartum Black Women in Brazil through structural racism lens 

Artigo mostra as diferenças étnico raciais de mortalidade materna durante a pandemia de COVID-19 no Brasil. Publicado originalmente no Oxford Academic. Acesse.

Disproportionate impact of COVID-19 among pregnant and postpartum Black Women in Brazil through structural racism lens 

Clinical Infectious Diseases, ciaa1066, https://doi.org/10.1093/cid/ciaa1066
Published: 28 July 2020

Transplacental transmission of SARS-CoV-2 infection

Transplacental transmission of SARS-CoV-2 infection

Publicado originamente no Nature (em inglês). DOI: 10.1038/s41467-020-17436-6

Abstract

SARS-CoV-2 outbreak is the first pandemic of the century. SARS-CoV-2 infection is transmitted through droplets; other transmission routes are hypothesized but not confirmed. So far, it is unclear whether and how SARS-CoV-2 can be transmitted from the mother to the fetus. We demonstrate the transplacental transmission of SARS-CoV-2 in a neonate born to a mother infected in the last trimester and presenting with neurological compromise. The transmission is confirmed by comprehensive virological and pathological investigations. In detail, SARS-CoV-2 causes: (1) maternal viremia, (2) placental infection demonstrated by immunohistochemistry and very high viral load; placental inflammation, as shown by histological examination and immunohistochemistry, and (3) neonatal viremia following placental infection. The neonate is studied clinically, through imaging, and followed up. The neonate presented with neurological manifestations, similar to those described in adult patients.

Introduction

SARS-CoV-2 infection causes the new coronavirus disease (COVID-19) and is mainly transmitted through droplets, but other transmission routes have been hypothesized. Some cases of perinatal transmission have been described1,2,3,4,5,6, but it is unclear if these occurred via the transplacental or the transcervical route or through environmental exposure. It is important to clarify whether and how SARS-CoV-2 reaches the fetus, so as to prevent neonatal infection, optimize pregnancy management and eventually better understand SARS-CoV-2 biology. Here we present a comprehensive case study demonstrating the transplacental transmission of SARS-CoV-2 with clinical manifestation in the neonate, consistent with neurological signs and symptoms of COVID-19.

Results

Case study

A 23-year-old, gravida 1, para 0 was admitted to our university hospital in March 2020 at 35+2 weeks of gestation with fever (38.6 °C) and severe cough and abundant expectoration since 2 days before hospitalisation. Real-time polymerase chain reaction (RT-PCR) was performed as described in the “Methods” below: both the E and S genes of SARS-CoV-2 were detected in blood, and in nasopharyngeal and vaginal swabs. Pregnancy was uneventful and all the ultrasound examinations and routine tests were normal until the diagnosis of COVID-19. Thrombocytopenia (54 × 109/L), lymphopenia (0.54 × 109/L), prolonged APTT (60 s), transaminitis (AST 81 IU/L; ALT 41 IU/L), elevated C-reactive protein (37 mg/L) and ferritin (431 μg/L) were observed upon hospital admission. Three days after admission a category III-fetal heart rate tracing7 (Fig. 1) was observed and therefore category II-cesarean section (i.e., fetal compromise; not immediately life-threatening, https://www.rcog.org.uk/globalassets/documents/guidelines/goodpractice11classificationofurgency.pdf) was performed, with intact amniotic membranes, in full isolation and under general anesthesia due to maternal respiratory symptoms. Clear amniotic fluid was collected prior to rupture of membranes, during cesarean section and tested positive for both the E and S genes of SARS-CoV-2. Delayed cord clamping was not performed as its effect on SARS-CoV-2 transmission is unknown. The woman remained hospitalized for surveillance of her clinical conditions and finally she was discharged in good conditions, 6 days after delivery.

Fig. 1: Illustrative snapshot of fetal heart rate tracing.
figure1

Tachycardia, absent baseline variability, absence of accelerations with recurrent prolonged and late decelerations. These findings are highly suggestive of a pathological category III fetal heart rate tracing7, which is strongly associated with adverse neonatal outcome. This cardiotogram was recorded 26 min before the cesarean section.

A male neonate was delivered (gestational age 35+5 weeks; birth weight 2540 g). Apgar scores were 4 (in detail: heart rate = 1, respiratory activity = 1, skin color = 1, muscular tonus = 1, remaining items were coded zero), 2 (in detail: skin color = 1, muscular tonus = 1, remaining items were coded zero) and 7 (in detail: heart rate = 2, respiratory activity = 2, skin color = 2, muscular tonus = 1) at 1, 5 and 10 min, respectively. Neonatal resuscitation was provided according to current international guidelines8 (face mask-delivered non-invasive ventilation from birth until 5 min of life and then intubation and invasive ventilation with inspired oxygen fraction titrated up to 0.30; monitoring included ECG, end-tidal side-stream CO2 measurements, peripheral oxygen saturation and perfusion index). The neonate was eventually transferred in full isolation to the neonatal intensive care unit (NICU) in a negative pressure room. Cord blood gas analysis showed normal pH and lactate. The neonate did not receive any sedative or analgesic drug and was monitored according to our routine NICU protocols for post-resuscitation care: Sarnat score, point-of-care echocardiography and lung ultrasound9 were normal upon NICU admission. Vital parameters were always normal and the baby was extubated after ~6 h. Before the extubation, blood was drawn for capillary blood gas analysis (at 1.5 h of life) and routine blood tests, which yielded normal values. Moreover, before the extubation, blood and non-bronchoscopic bronchoalveolar lavage fluid were collected for RT-PCR and both were positive for the E and S genes of SARS-CoV-2. Lavage was performed using a standardized procedure10 as detailed below. Blood culture was negative for bacteria or fungi. Nasopharyngeal and rectal swabs were first collected after having cleaned the baby at 1 h of life, and then repeated at 3 and 18 days of postnatal age: they were tested with RT-PCR and were all positive for the two SARS-CoV-2 genes. Routine blood tests (including troponin, liver and kidney function) were repeated on the second day of life and resulted normal. Feeding was provided exclusively using formula milk.

On the third day of life, the neonate suddenly presented with irritability, poor feeding, axial hypertonia and opisthotonos: cerebrospinal fluid (CSF) was negative for SARS-CoV-2, bacteria, fungi, enteroviruses, herpes simplex virus 1 and 2, showed normal glycorrhachia albeit with 300 leukocytes/mm3 and slightly raised proteins (1.49 g/L). Blood was taken at the same time and the culture was sterile. Cerebral ultrasound and EEG were also normal. There were no signs suspected for metabolic diseases. Symptoms improved slowly over 3 days and a second CSF sample was normal on the fifth day of life, but mild hypotonia and feeding difficulty persisted. Main laboratory findings are resumed in Table 1. Magnetic resonance imaging at 11 days of life showed bilateral gliosis of the deep white periventricular and subcortical matter, with slightly left predominance (Fig. 2). The neonate did not receive antivirals or any other specific treatment, gradually recovered and was finally discharged from hospital after 18 days. Follow-up at almost 2 months of life showed a further improved neurological examination (improved hypertonia, normal motricity) and magnetic resonance imaging (reduced white matter injury); growth and rest of clinical exam were normal.

Table 1 Main laboratory findings in the neonate.
Fig. 2: Cerebral MRI performed at 11 days of life.
figure2

ab and cd T1 and diffusion-weighted sequences, respectively. Images are taken at two different levels and show hyperintensities of the periventricular and subcortical frontal or parietal white matter (arrows).

Virology and pathology

RT-PCR on the placenta was positive for both SARS-CoV-2 genes. Figure 3 shows all RT-PCR results obtained in different maternal and neonatal specimens: viral load was much higher in placental tissue, than in amniotic fluid and maternal or neonatal blood.

Fig. 3: Real-time polymerase chain reaction results.
figure3

ab The E and S genes of SARS-CoV-2, respectively, for maternal and neonatal samples (X and Y axes represent the amount of amplified RNA and the number of cycles, respectively; the earlier the signal is detected, the lowest is the number of cycles and the higher the viral load is). c The viral load for each sample (expressed as Log copies/million of cells for the placenta and as Log copies/mL for all other specimens). All maternal samples were obtained right before the delivery or during C-section; newborn samples are listed chronologically and were obtained from the first to the third day of life, except for the last nasopharyngeal swab (obtained at 18 days of postnatal age). Colored lines represent the results of RT-PCR assay for each sample. The deep orange line represents the positive control, which is a SARS-CoV-2 culture supernatant (more details in “Methods”). Nasopharyngeal swabs at 1, 3 and 18 day of life are represented by the light orange, gray and green curves, respectively. Viral load in BAL fluidis not shown. DOL days of life, M maternal samples, Nb newborn samples.

Placental histological examination was performed as described in “Methods” below and revealed diffuse peri-villous fibrin deposition with infarction and acute and chronic intervillositis. An intense cytoplasmic positivity of peri-villous trophoblastic cells was diffusely observed performing immunostaining with antibody against SARS-CoV-2 N-protein. No other pathogen agent was detected on special stains and immunohistochemistry. Figures 4 and 5 depict the results of the placental gross and microscopic examination, as well as immunohistochemistry.

Fig. 4: Gross and microscopic examination of the placenta.
figure4

a The macroscopic lesions of perivillous fibrin deposition with infarction, as irregular strands of pale yellow-white induration (arrow). b Microscopic lesions of intervillositis characterized by an infiltrate of the intervillous spaces made of neutrophils and histiocytes (arrow) (HES stain, original magnification ×400). c The intervillositis with several CD68-positive histiocytes (arrow); neutrophils are negative with this anti-macrophage antibody (anti-CD68 immunohistochemistry, original magnification ×400).

Fig. 5: Placental immunostaining for SARS-CoV-2 N-protein (anti-N immunohistochemistry, original magnification ×800).
figure5

a The intense brown cytoplasmic positivity of peri-villous trophoblastic cells in the placenta of our case (arrows). bc Two negative controls (primary antibody, two SARS-CoV-2 negative placentas).

Discussion

We report a proven case of transplacental transmission of SARS-CoV-2 from a pregnant woman affected by COVID-19 during late pregnancy to her offspring. Other cases of potential perinatal transmission have recently been described, but presented several unaddressed issues. For instance, some failed to detect SARS-CoV-2 in neonates or only reported the presence of specific antibodies1,2,4; others found the virus in the newborn samples but the transmission route was not clear as placenta, amniotic fluid and maternal or newborn blood were not systematically tested in every mother-infant pair3,5,6,11,12.

A classification for the case definition of SARS-CoV-2 infection in pregnant women, fetuses and neonates has recently been released and we suggest to follow it to characterize cases of potential perinatal SARS-CoV-2 transmission. According to this classification system, a neonatal congenital infection is considered proven if the virus is detected in the amniotic fluid collected prior to the rupture of membranes or in blood drawn early in life, so our case fully qualifies as congenitally transmitted SARS-CoV-2 infection, while the aforementioned cases would be classified as only possible or even unlikely13. Another recent report describes a case with similar placental findings, but it has been classified only as probable case of congenital SARS-CoV-2 infection, because cord and newborn blood could have not been tested14.

Both “E” and “S” gene of SARS-CoV-2 were found in each and every specimen, thus they were considered all positive, according to the European Centre for Disease Control recommendations (https://www.ecdc.europa.eu/en/all-topics-z/coronavirus/threats-and-outbreaks/covid-19/laboratory-support/questions). Of note, the viral load is much higher in the placental tissue than in amniotic fluid or maternal blood: this suggests the presence of the virus in placental cells, which is consistent with findings of inflammation seen at the histological examination. Finally, the RT-PCR curves of neonatal nasopharyngeal swabs at 3 and 18 day of life are higher than that at the first day (while the baby was in full isolation in a negative pressure room): this is also another confirmation that we observed an actual neonatal infection, rather than a contamination. Thus, these findings suggest that: (1) maternal viremia occurred and the virus reached the placenta as demonstrated by immunohistochemistry; (2) the virus is causing a significant inflammatory reaction as demonstrated by the very high viral load, the histological examination and the immunohistochemistry; (3) neonatal viremia occurred following placental infection. Our findings are also consistent with a case study describing the presence of virions in placental tissue, although this did not report neither placental inflammation, nor fetal/neonatal infection15.

The placenta showed signs of acute and chronic intervillous inflammation consistent with the severe systemic maternal inflammatory status triggered by SARS-CoV-2 infection. As RT-PCR on the placental tissue was positive for SARS-CoV-2, and both maternal and neonatal blood samples were also positive, the transmission clearly occurred through the placenta. Interestingly, placentas from women affected by SARS-CoV-1 presented similar pathological findings of intervillositis, with intervillous fibrin deposition16. Angiotensin-converting enzyme 2 (ACE2) is known to be the receptor of SARS-CoV-2 and is highly expressed in placental tissues17. Animal data show that ACE2 expression changes in fetal/neonatal tissues over time and reaches a peak between the end of gestation and the first days of postnatal life17. The combination of these data and our findings confirms that transplacental transmission is indeed possible in the last weeks of pregnancy, although we cannot exclude a possible transmission and fetal consequences earlier during the pregnancy, as there are no definite literature data available yet.

Interestingly, we described a case of congenital infection associated with neurological manifestations following neonatal viremia. Suspected neonatal SARS-CoV-2 infections presented with non-specific symptoms4 or pneumonia3, while neurological symptoms are commonly observed in adult patients, especially due to the inflammatory response18,19. Early neurological manifestations were also observed in another neonate born to SARS-CoV-2 positive mother, although vertical transmission was not fully investigated12. Conversely, after the viremia, our case clearly presented neurological symptoms and inflammatory findings in CSF. There was no other viral or bacterial infection and all other neonatal disorders potentially causing these clinical manifestations were excluded. Neuroimaging consistently indicated white matter injury, which can be caused by the vascular inflammation induced by SARS-CoV-2 infection, as similar images have been anecdotally found in adult patients20,21.

In conclusion, we have demonstrated that the transplacental transmission of SARS-CoV-2 infection is possible during the last weeks of pregnancy. Transplacental transmission may cause placental inflammation and neonatal viremia. Neurological symptoms due to cerebral vasculitis may also be associated.

Methods

Patient sampling

Biological samples to be tested by RT-PCR were obtained and prepared as follows. Nasopharyngeal and vaginal swabs were obtained following US Center for Disease Control and Prevention guidelines (https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.htmlhttps://www.cdc.gov/groupbstrep/downloads/gbs_swab_sheet21.pdf). A sample of placental tissues was taken from the chorionic side and crushed in 400 mL of RNAase-DNAase-free water; 1 mL of blood and swabs were placed in Virocult® viral transport media (Sigma, St. Louis, MI, USA). Non-bronchoscopic bronchoalveolar lavage (BAL) was performed following a well-known standardized technique10: in detail, the neonate was placed supine with the head turned to the right so that the left lung would be predominantly sampled. Normal saline (1 mL/kg, 37 °C) was instilled into the endotracheal tube through a Y-piece. After three ventilator cycles, the suction catheter was gently inserted 0.5 cm beyond the tube tip, and the airway fluid was aspirated into a sterile specimen trap (BALF Trap; Vigon, Ecouen, France) with 50 mmHg of negative pressure. This procedure was repeated with the head turned to the left, so that the right lung would be predominantly sampled. This procedure respects European Respiratory Society advices for pediatric and neonatal BAL22. During the procedure, the patient was never disconnected from the ventilator, the inspired oxygen fraction was 0.25 and there was no desaturation or bradycardia. All specimens were kept at +4 °C and tested within 24 h.

Real-time polymerase chain reaction (RT-PCR)

Viral RNA was extracted from 200 µL clinical samples with the NucliSENS® easyMag® (BioMérieux, Craponne, France) and eluted in 100 µL. The RealStar® SARS-CoV-2 RT-PCR Kit 1.0 (Altona Diagnostics GmbH, Hamburg, Germany) targeting the E gene (specific for lineage B-betacoronavirus) and the S gene (specific for SARS-CoV-2) was used following the manufacturer’s recommendations (https://altona-diagnostics.com/en/products/reagents-140/reagents/realstar-real-time-pcr-reagents/realstar-sars-cov-2-rt-pcr-kit-ruo.html). The assay includes a heterologous amplification system (internal positive control) to identify possible RT-PCR inhibition and to confirm the integrity of the reagents of the kit. The positive control is a SARS-CoV-2 culture supernatant provided by the kit manufacturer. Thermal cycling was performed at 55 °C for 20 min for reverse transcription, followed by 95 °C for 2 min and then 45 cycles of 95 °C for 15 s, 55 °C for 45 s, 72 °C for 15 s with an Applied Biosystems ViiA7 instrument (Applied Biosystems, Thermo Fisher, Waltham, MA, USA). A cycle threshold value less than 40 is interpreted as positive for SARS-CoV-2 RNA. Our technique resulted to have an extremely low limit of detection (LOD = 1200 cp/mL (12 cp/rxn)). Reproducibility and inter-assay agreement were 100% both for negative and for positive tests, against two other common techniques23.

Placental examination

Placental sampling, gross and microscopic examination were performed according to the Amsterdam Consensus statement24. The placenta was fixed in 4% buffered formalin and samples were paraffin embedded. Staining methods performed on 3–5 µm thick sections were: haemalun eosin saffran, periodic acid schiff and Gomori-Grocott stains. Immunohistochemistry with peroxydase detection and hemalun counterstain was performed in a Leica Bond III automat using the Bond Polymer Refine Detection kit (Leica DS9800) after heat pretreatment at pH6 or 9 depending on the monoclonal antibodies tested: CD68 (Dako PG-M1, 1:200), CD163 (Leica 10D6, 1:200), CD20 (Dako L26, 1:400), CD3 (Dako F7.2.38, 1:50), CD5 (Novocastra 4C7, 1:50), CMV (Dako CCH2 + DDG9, 1:1), Parvo virus (AbcVs, Abc10-P038), SARS-CoV-2 (Abclonal, rabbit pAB, 2019-nCoV N Protein, 1:2400). Negative controls for SARS-CoV-2 immunohistochemistry were done: control of the polyclonal rabbit primary antibody, SARS-CoV-2 negative placental specimen with similar pre-analytic conditions of formalin fixation.

Ethics declaration

Written informed consent was obtained from the woman for the publication of this report. According to French regulation, institutional review board (IRB) approval is not required for case reports, provided that patients’ written consent is obtained. The French Ethical Committee for the Research in Obstetrics and Gynecology reviewed the work and confirmed that the IRB approval was unnecessary. The case study was performed in agreement with principles of the Declaration of Helsinki and CARE guidelines25.

Reporting summary

Further information on research design is available in the Nature Research Reporting Summary linked to this article.

Data availability

All data generated or analyzed during this study are included in this published article.

References

  1. 1.

    Zeng, H. et al. Antibodies in infants born to mothers with COVID-19 pneumonia. JAMA 323, 1848–1849 (2020).

    CAS PubMed Central Google Scholar

  2. 2.

    Dong, L. et al. Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn. JAMA 323, 1846–1848 (2020).

    CAS PubMed Central Google Scholar

  3. 3.

    Zeng, L. et al. Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China. JAMA Pediatr. https://doi.org/10.1001/jamapediatrics.2020.0878 (2020).

    Article PubMed Google Scholar

  4. 4.

    Zhu, H. et al. Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia. Transl. Pediatr. 9, 51–60 (2020).

    Article Google Scholar

  5. 5.

    Yu, N. et al. Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect. Dis. 20, 559–564 (2020).

    CAS Article Google Scholar

  6. 6.

    Alzamora, M. C. et al. Severe COVID-19 during Pregnancy and possible vertical transmission. Am. J. Perinatol. https://doi.org/10.1055/s-0040-1710050 (2020).

    Article PubMed Google Scholar

  7. 7.

    American College of Obstetricians and Gynecologists. Practice bulletin no. 106: intrapartum fetal heart rate monitoring: nomenclature, interpretation, and general management principles. Obstet. Gynecol. 114, 192–202 (2009).

    Article Google Scholar

  8. 8.

    Perlman, J. M. et al. Part 7: neonatal resuscitation: 2015 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations (Reprint). Pediatrics 136, S120–S166 (2015).

    Article Google Scholar

  9. 9.

    Singh, Y. et al. International evidence-based guidelines on point of care ultrasound (POCUS) for critically ill neonates and children issued by the POCUS Working Group of the European Society of Paediatric and Neonatal Intensive Care (ESPNIC). Crit. Care 24, 65 (2020).

    Article Google Scholar

  10. 10.

    De Luca, D. et al. Role of distinct phospholipases A2 and their modulators in meconium aspiration syndrome in human neonates. Intensiv. Care Med. 37, 1158–1165 (2011).

    Article Google Scholar

  11. 11.

    Zamaniyan, M. et al. Preterm delivery in pregnant woman with critical COVID ‐19 pneumonia and vertical transmission. Prenat. Diag. https://doi.org/10.1002/pd.5713 (2020).

    Article Google Scholar

  12. 12.

    Lorenz, N. et al. Neonatal early-onset infection with SARS-CoV-2 in a newborn presenting with encephalitic symptoms. Pediat. Infect. Dis. J1https://doi.org/10.1097/INF.0000000000002735 (2020).

  13. 13.

    Shah, P. S., Diambomba, Y., Acharya, G., Morris, S. K. & Bitnun, A. Classification system and case definition for SARS-CoV-2 infection in pregnant women, fetuses, and neonates. Acta Obstet. Gynecol. Scand. 99, 565–568 (2020).

    CAS Article Google Scholar

  14. 14.

    Kirtsman, M. et al. Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. CMAJ https://doi.org/10.1503/cmaj.200821 (2020).

    Article PubMed Google Scholar

  15. 15.

    Algarroba, G. N. et al. Visualization of SARS-CoV-2 virus invading the human placenta using electron microscopy. Am. J. Obstet. Gynecol. https://doi.org/10.1016/j.ajog.2020.05.023 (2020).

    Article PubMed PubMed Central Google Scholar

  16. 16.

    Ng, W. F. et al. The placentas of patients with severe acute respiratory syndrome: a pathophysiological evaluation. Pathology 38, 210–218 (2006).

    CAS Article Google Scholar

  17. 17.

    Li, M., Chen, L., Zhang, J., Xiong, C. & Li, X. The SARS-CoV-2 receptor ACE2 expression of maternal-fetal interface and fetal organs by single-cell transcriptome study. PLoS ONE 15, e0230295 (2020).

    CAS Article Google Scholar

  18. 18.

    Mao, L. et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol. 77, 1–9 (2020).

    Article Google Scholar

  19. 19.

    Needham, E. J., Chou, S. H.-Y., Coles, A. J. & Menon, D. K. Neurological implications of COVID-19 infections. Neurocrit. Care 32, 667–671 (2020).

    CAS Article Google Scholar

  20. 20.

    Poyiadji, N. et al. COVID-19–associated acute hemorrhagic necrotizing encephalopathy: CT and MRI features. Radiology 201187, https://doi.org/10.1148/radiol.2020201187 (2020).

  21. 21.

    Moriguchi, T. et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int. J. Infect. Dis. 94, 55–58 (2020).

    CAS Article Google Scholar

  22. 22.

    De Blic, J. et al. Bronchoalveolar lavage in children. ERS Task Force on bronchoalveolar lavage in children. European Respiratory Society. Eur. Resp. J. 15, 217–231 (2000).

    Article Google Scholar

  23. 23.

    Uhteg, K. et al. Comparing the analytical performance of three SARS-CoV-2 molecular diagnostic assays. J. Clin. Virol. 127, 104384 (2020).

    CAS Article Google Scholar

  24. 24.

    Khong, T. Y. et al. Sampling and definitions of placental lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch. Pathol. Lab. Med. 140, 698–713 (2016).

    Article Google Scholar

  25. 25.

    Riley, D. S. et al. CARE guidelines for case reports: explanation and elaboration document. J. Clin. Epidemiol. 89, 218–235 (2017).

    Article Google Scholar

Transplacental transmission of SARS-CoV-2 infection
Author: Alexandre J. Vivanti et al
Publication: Nature Communications
Publisher: Springer Nature
Date: Jul 14, 2020

Characteristics and Outcomes of Pregnant Women Admitted to Hospital With Confirmed SARS-CoV-2 Infection in UK: National Population Based Cohort Study

Acesse o original: https://pubmed.ncbi.nlm.nih.gov/32513659/

Characteristics and Outcomes of Pregnant Women Admitted to Hospital With Confirmed SARS-CoV-2 Infection in UK: National Population Based Cohort Study

Affiliations

Free PMC article

Abstract

Objectives: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants.

Design: Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS).

Setting: All 194 obstetric units in the UK.

Participants: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020.

Main outcome measures: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission.

Results: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth.

Conclusions: Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation.

Study registration: ISRCTN 40092247.

Preeclampsia-like Syndrome Induced by Severe COVID-19: A Prospective Observational Study

Preeclampsia-like Syndrome Induced by Severe COVID-19: A Prospective Observational Study

Abstract

Objectives: To investigate the incidence of clinical, ultrasonographic and biochemical findings related to preeclampsia (PE) in pregnancies with COVID-19, and to assess their accuracy to differentiate between PE and the PE-like features associated with COVID-19.

Design: A prospective, observational study.

Setting: Tertiary referral hospital.

Participants: Singleton pregnancies with COVID-19 at >20+0 weeks.

Methods: 42 consecutive pregnancies were recruited and classified into two groups: severe and nonsevere COVID-19, according to the occurrence of severe pneumonia. Uterine artery pulsatility index (UtAPI) and angiogenic factors (soluble fms-like tyrosine kinase-1/placental growth factor [sFlt-1/PlGF]) were assessed in women with suspected PE.

Main outcome measures: Incidence of signs and symptoms related to PE, such as hypertension, proteinuria, thrombocytopenia, elevated liver enzymes, abnormal UtAPI and increased sFlt-1/PlGF.

Results: 34 cases were classified as nonsevere and 8 as severe COVID-19. Six (14.3%) women presented signs and symptoms of PE, all six being among the severe COVID-19 cases (75.0%). However, abnormal sFlt-1/PlGF and UtAPI could only be demonstrated in one case. Two cases remained pregnant after recovery from severe pneumonia and had a spontaneous resolution of the PE-like syndrome.

Conclusions: Pregnant women with severe COVID-19 can develop a PE-like syndrome that might be distinguished from actual PE by sFlt-1/PlGF, LDH and UtAPI assessment. Health care providers should be aware of its existence and monitor pregnancies with suspected preeclampsia with caution.

Keywords: COVID-19; PlGF; SARS; SARS-CoV-2; angiogenic factors; preeclampsia; preeclampsia-like syndrome; pregnancy; sFlt-1.

Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain

Publicado originalmente no JAMA Network. Acesse o original (em inglês)
JAMA. Published online June 8, 2020. doi:10.1001/jama.2020.10125
Data from China found severe complications in 8% of pregnant women with coronavirus disease 2019 (COVID-19).1 However, the high rate of cesarean deliveries (>90%) in Chinese reports is concerning,2 and whether mode of delivery is associated with maternal complications or neonatal transmission is unknown.3 We assessed births to women with COVID-19 by mode of delivery.

Caring for Women Who Are Planning a Pregnancy, Pregnant, or Postpartum During the COVID-19 Pandemic

Caring for Women Who Are Planning a Pregnancy, Pregnant, or Postpartum During the COVID-19 Pandemic

JAMA. Published online June 5, 2020. doi:10.1001/jama.2020.8883

Acesse o original
AB – Since its recognition in China in December 2019, coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world and become a pandemic. Although considerable data on COVID-19 are available, much remains to be learned about its effects on pregnant women and newborns.No data are currently available to assess whether pregnant women are more susceptible to COVID-19. Pregnant women are at risk for severe disease associated with other respiratory illnesses (eg, 2009 H1N1 influenza), but thus far, pregnant women with COVID-19 do not appear to be at increased risk for severe disease compared with the general population. Data from China showed that among 147 pregnant women, 8% had severe disease and 1% had critical illness, which are lower rates than observed in the nonpregnant population (14% with severe disease and 6% with critical illness). Case series from China consisting primarily of women with third-trimester infection have shown that clinical findings in pregnant women are similar to those seen in the general population. Conversely, a small Swedish study reported that pregnant and postpartum women with COVID-19 were 5 times more likely to be admitted to an intensive care unit compared with nonpregnant women of similar age.

Provider: Silverchair
Database: AmericanMedicalAssociation

Pesquisa inédita da UFC revela níveis elevados de estresse e risco de depressão em gestantes no distanciamento

Publicado originalmente no Portal da UFC – Universidade Federal do Ceará

Imagem: Mais de mil mulheres grávidas em isolamento social participaram da pesquisa (Foto: Marcello Casal Jr./ABr)

Pesquisa inédita da Universidade Federal do Ceará revelou níveis elevados de estresse e risco de depressão em mulheres grávidas de Fortaleza, no período de distanciamento social decorrente da COVID-19. Coordenado pela Profª Márcia Machado, da Faculdade de Medicina da UFC, o estudo mostrou que cerca de 43% das gestantes demonstram medo, ansiedade e transtornos do comportamento, índice considerado alto, se comparado com a média de 25% detectada em pesquisas realizadas em outros períodos, a exemplo da Pesquisa de Saúde Materno-Infantil no Ceará/UFC (PESMIC).

O estudo “Gravidez durante a COVID-19 em Fortaleza, Ceará: percepção materna sobre saúde, expectativas, medo e os cuidados prestados ao filho”, realizado de forma on-line durante o período de distanciamento, contou com a participação de 1.041 mulheres, abrangendo todas as regionais administrativas da Capital. A pesquisa utilizou como parâmetros duas escalas sobre saúde mental (SRQ e “Fear of COVID-19”).

As gestantes responderam aos questionários enviados pelo WhatsApp e outras redes sociais, com apoio de lideranças comunitárias e de serviços do Estado e do Município. Resultados preliminares apontam que 84,3% sentem desconforto ao pensar na COVID-19; 74,6% sentem-se assustadas ao pensar no coronavírus; 18,7% não conseguem dormir; 75,3% sentem-se nervosas ao assistir a notícias na televisão; 49,8% têm chorado mais do que o costume; e 57,9% têm se sentido triste ultimamente.

Das 1.041 mulheres, 335 afirmaram ter filhos de 1 a 5 anos completos. Perguntadas sobre como agiram com os filhos nos 15 dias anteriores ao preenchimento do questionário, 18,8% disseram ter batido no filho; 70,6% ter gritado; 20,1% ter puxado a orelha, dado tapa ou batido na mão. Para a Profª Márcia Machado, os dados são reveladores do nível de estresse no período de isolamento, se comparados com outros estudos que costumam avaliar a saúde mental de grávidas em períodos “normais”.

Imagem: A Profª Márcia Machado, da Faculdade de Medicina, é a coordenadora da pesquisa (Foto: Viktor Braga/UFC)

A pesquisadora chama a atenção para o fato de a maioria das respondentes ser casada (ou viver em união estável) e ter pelo menos o ensino médio concluído: “Se essa população que tem níveis de escolaridade maior e vive com um companheiro apresentou nível elevado de estresse, podemos imaginar como estão as mulheres que vivem em situação de extrema pobreza“, reflete a Profª Márcia.

Transtornos psicológicos ou psiquiátricos na gravidez podem trazer consequências para a saúde da mulher e do bebê. Segundo a pesquisadora, há relação entre esses fatores e a maior incidência de partos prematuros ou de crianças nascidas com baixo peso, por exemplo.

Além disso, o nível de estresse pode acarretar maiores níveis de agressividade com filhos e parceiros, o que também prejudica o desenvolvimento infantil. Márcia aponta, portanto, para a necessidade da criação de protocolos especiais de atenção básica que garantam o acompanhamento de mulheres durante a gravidez e no pós-parto, neste período de pandemia.

Os dados completos da pesquisa deverão, em breve, ser publicados em periódicos nacionais e internacionais. Segundo a Profª Márcia, não há estudos semelhantes concluídos sobre essa situação específica de mulheres grávidas durante o distanciamento social. A proposta é ampliar essa pesquisa e acompanhar aquelas mulheres e seus bebês após o parto, por um período de três anos.

A pesquisa foi financiada pela Fundação Maria Cecília Souto Vidigal e contou com a participação de estudantes de pós-graduação da UFC (Camila Machado de Aquino, Jordan Prazeres Freitas, Francisco Ariclene Oliveira, Edgar Sampaio); de professores dos departamentos de Saúde Pública e de Saúde Materno-Infantil da UFC (Luciano Lima Correia, Hermano Lima Rocha, Herlânio Costa Carvalho); da presidente da Associação de Ginecologistas e Obstetras do Ceará, Liduina de Albuquerque Rocha de Sousa; da professora da Universidade de Ribeirão Preto Elisa Altafim; e da professora da Harvard T.H Chan School of Public Health, Marcia C. Castro.

PALESTRA NOS EU2019 – A Profª Marcia Machado, coordenadora da pesquisa, será a mediadora da palestra magna dos Encontros Universitários 2019, nesta quarta-feira (20), às 10h. A palestra “Pandemia e a saúde coletiva” será realizada pela Profª Marcia C Castro, da Harvard T.H. Chan School of Public Health, membra do Programa de Estudos Brasileiros no Centro David Rockefeller para Estudos Latino-Americanos e membra do comitê de direção do Centro de Análises Geográficas.

OS EU2019 ocorrerão em formato virtual. O link para a transmissão ao vivo da palestra magna será disponibilizado em breve.

Fonte: Profª Márcia Machado, do Departamento de Saúde Comunitária da Faculdade de Medicina da UFC – e-mail: marciamachadoufc@gmail.com

Gravidez, nascimento e a pandemia de COVID-19 nos Estados Unidos

Acesse o original (em inglês)

Pregnancy, Birth and the COVID-19 Pandemic in the United States

Published online: 14 May 2020

How quickly and in what ways are US maternity care practices changing due to the COVID-19 pandemic? Our data indicate that partners and doulas are being excluded from birthing rooms leaving mothers unsupported, while providers face lack of protective equipment and unclear guidelines. We investigate rapidly shifting protocols for in- and out-of-hospital births and the decision making behind them. We ask, will COVID-19 cause women, families, and providers to look at birthing in a different light? And will this pandemic offer a testing ground for future policy changes to generate effective maternity care amidst pandemics and other types of disasters?