ABSTRACT

A rapid systematic review was carried out to evaluate the current evidence related to the presence of SARS-CoV-2 in breast milk from pregnant women with COVID-19. Eight studies analyzing the presence of SARS-CoV-2 RNA in the breast milk of 24 pregnant women with COVID-19 during the third trimester of pregnancy were found. All patients had fever and/or symptoms of acute respiratory illness and chest computed tomography images indicative of COVID-19 pneumonia. Most pregnant women had cesarean delivery (91.7%) and two neonates had low birthweight (< 2 500 g). Biological samples collected immediately after birth from upper respiratory tract (throat or nasopharyngeal) of neonates and placental tissues showed negative results for the presence SARS-CoV-2 by RT-PCR test. No breast milk samples were positive for SARS-CoV-2 and, to date, there is no evidence on the presence of SARS-CoV-2 in breast milk of pregnant women with COVID-19. However, data are still limited and breastfeeding of women with COVID-19 remains a controversial issue. There are no restrictions on the use of milk from a human breast milk bank.

Keywords
Coronavirus infection; virus diseases; pneumonia, viral; pandemics; SARS virus; breast feeding

RESUMEN

Se llevó a cabo una revisión sistemática rápida para evaluar la evidencia disponible sobre la presencia de SARS-CoV-2 en la leche materna de mujeres embarazadas afectadas con COVID-19. Se encontraron ocho estudios que analizaron la presencia de ARN de SARS-CoV-2 en la leche materna de 24 mujeres embarazadas con COVID-19 durante el tercer trimestre del embarazo. Todas las pacientes tenían fiebre o síntomas de enfermedad respiratoria aguda e imágenes de tomografía computarizada de tórax indicativas de neumonía por COVID-19. La mayoría de las mujeres embarazadas (91,7%) tuvieron un parto por cesárea y dos neonatos presentaron bajo peso al nacer (< 2 500 g). Las muestras biológicas recogidas inmediatamente después del parto de las vías respiratorias superiores (faringe o nasofaringe) de los neonatos y los tejidos placentarios mostraron resultados negativos para SARS-CoV-2 mediante RT-PCR. Ninguna muestra de leche materna fue positiva para SARS-CoV-2 y, hasta la fecha, no hay evidencia de la presencia de SARS-CoV-2 en la leche materna de las mujeres embarazadas con COVID-19. Sin embargo, los datos disponibles todavía son limitados y la lactancia materna en las mujeres con COVID-19 sigue siendo un tema controvertido. No hay restricciones para el uso de leche materna de banco.

Palabras clave
Infecciones por coronavirus; virosis; pandemias; virus del SRAS; lactancia materna

RESUMO

Foi realizada uma revisão sistemática rápida para avaliar as evidências atuais relacionadas à presença da SARS-CoV-2 no leite materno de mulheres grávidas com COVID-19. Foram encontrados oito estudos analisando a presença de RNA do SARS-CoV-2 no leite materno de 24 gestantes com COVID-19 durante o terceiro trimestre de gravidez. Todas as pacientes apresentavam febre ou sintomas de doença respiratória aguda e imagens de tomografia computadorizada do tórax indicativas de pneumonia pela COVID-19. A maioria das gestantes teve parto cesáreo (91,7%) e dois recém-nascidos tiveram baixo peso ao nascer (< 2 500 g). As amostras biológicas coletadas imediatamente após o nascimento do trato respiratório superior (faringe ou nasofaringe) de neonatos e tecidos placentários apresentaram resultados negativos para a presença do SARS-CoV-2 pelo teste RT-PCR. Nenhuma amostra de leite materno foi positiva para o SARS-CoV-2 e, até à data, não há evidências da presença do SARS-CoV-2 no leite materno de mulheres grávidas com COVID-19. No entanto, os dados ainda são limitados e a amamentação de mulheres com COVID-19 continua a ser uma questão controversa. Não há restrições ao uso de leite de um banco de leite materno humano.

Palavras-chave
Infecções por coronavirus; viroses; pandemias; vírus da SARS; aleitamento materno

SARS-CoV-2 is a novel emerged positive-strand RNA virus associated with an acute respiratory distress disease known as COVID-19. Studies have suggested that transmission of SARS-CoV-2 is primarily from person to person through respiratory droplets (¹1. Chan JF-W, Yuan S, Kok K-H, To KK-W, Chu H, Yang J, et al. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: a study of a family cluster. Lancet. 2020 Feb;395(10223):514-23.,²2. Ghinai I, McPherson TD, Hunter JC, Kirking HL, Christiansen D, Joshi K, et al. First known person-to-person transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the USA. Lancet [Internet]. 2020 Mar 13; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32178768
http://www.ncbi.nlm.nih.gov/pubmed/32178... ). In addition, there is emergent evidence that the virus could be detected in biological fluids including bronchoalveolar lavage fluid specimens (³3. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA [Internet]. 2020 Mar 11; Available from: https://jamanetwork.com/journals/jama/fullarticle/2762997
https://jamanetwork.com/journals/jama/fu... ), blood (³3. Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA [Internet]. 2020 Mar 11; Available from: https://jamanetwork.com/journals/jama/fullarticle/2762997
https://jamanetwork.com/journals/jama/fu... ,⁴4. Young BE, Ong SWX, Kalimuddin S, Low JG, Tan SY, Loh J, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA [Internet]. 2020 Mar 3; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32125362
http://www.ncbi.nlm.nih.gov/pubmed/32125... ) and saliva (⁵5. To KK-W, Tsang OT-Y, Chik-Yan Yip C, Chan K-H, Wu T-C, Chan JMC, et al. Consistent detection of 2019 novel coronavirus in saliva. Clin Infect Dis [Internet]. 2020 Feb 12; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32047895
http://www.ncbi.nlm.nih.gov/pubmed/32047... ), but substantial knowledge gaps remain regarding the presence of SARS-CoV-2 in the breast milk. Recently, a report in Science discussed the wrenching choices of pregnant women with COVID-19 after childbirth including whether or not they should breastfeed their children (⁶6. Vogel G. New coronavirus leaves pregnant women with wrenching choices—but little data to guide them. Science (80- ) [Internet]. 2020 Mar 27; Available from: https://www.sciencemag.org/news/2020/03/new-coronavirus-leaves-pregnant-women-wrenching-choices-little-data-guide-them
https://www.sciencemag.org/news/2020/03/... ).

METHODS

We performed a rapid systematic review to evaluate the current evidence related to the presence of SARS-CoV-2 in breast milk from pregnant women with COVID-19. The study was conducted in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines (⁷7. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Int J Surg [Internet]. 2010 Jan [cited 2014 Jul 10];8(5):336-41. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20171303
http://www.ncbi.nlm.nih.gov/pubmed/20171... ), but given emergency-need for this review, PROSPERO registration was not sought. Using terms related to coronavirus, we searched in PubMed, Web of Science, Scopus, China National Knowledge Infrastructure database, and grey literature (Google Scholar and preprint repositories) to identify studies reporting results of RT-PCR tests on breast milk in pregnant women with laboratory-confirmed SARS-CoV-2 infection. Searches were performed up to March 30, 2020 and updated on April 21, 2020.

RESULTS AND DISCUSSION

We found eight studies (⁸8. Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020;395(10226):809-15.–¹⁵15. Liu W, Wang J, Li W, Zhou Z, Liu S, Rong Z. Clinical characteristics of 19 neonates born to mothers with COVID-19. Front Med [Internet]. 2020 Apr 13; Available from: http://link.springer.com/10.1007/s11684-020-0772-y
http://link.springer.com/10.1007/s11684-... ) analyzing the presence of SARS-CoV-2 RNA in the breast milk of 24 pregnant women with COVID-19 during the third trimester of pregnancy (Table 1). All patients had fever and/or symptoms of acute respiratory illness and chest computed tomography (CT) images indicative of COVID-19 pneumonia. Most pregnant women had cesarean delivery (91.7%) and two neonates had low birthweight (< 2,500 g). Biological samples collected immediately after birth from upper respiratory tract (throat or nasopharyngeal) of neonates and placental tissues showed negative results for the presence SARS-CoV-2 by RT-PCR test. In addition, no breast milk samples were positive for SARS-CoV-2. In three studies (¹⁰10. Fan C, Lei D, Fang C, Li C, Wang M, Liu Y, et al. Perinatal Transmission of COVID-19 Associated SARS-CoV-2: Should We Worry? Clin Infect Dis [Internet]. 2020 Mar 17; Available from: https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa226/5809260
https://academic.oup.com/cid/advance-art... ,¹²12. Liu W, Wang Q, Zhang Q, Chen L, Chen J, Zhang B, et al. Coronavirus disease 2019 (COVID-19) during pregnancy: a case series. Preprints. 2020;(February):1-28.,¹³13. Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. A case report of neonatal COVID-19 infection in China. Clin Infect Dis [Internet]. 2020 Mar 12; Available from: http://www.ncbi.nlm.nih.gov/pubmed/32161941
http://www.ncbi.nlm.nih.gov/pubmed/32161... ) there was a clear recommendation for mother’s to not breastfeed their children despite the lack of evidence on the potential viral transmission via breast milk.

As the coronavirus pandemic takes hold, pregnant women infected with SARS-CoV-2 experience fear and uncertainties regarding the care of their child. Making decisions without a robust evidence base may influence mother-child interactions and lead to poor outcomes. Furthermore, there is a lack of consensus among health agencies regarding breastfeeding for women with COVID-19. In February 2020, the National Health Commission of China recommended that neonates of pregnant women with suspected or confirmed COVID-19 should be isolated in a designated unit for at least 14 days and should not be breastfeed due to the high risk of infection (¹⁶16. Wang L, Shi Y, Xiao T, Fu J, Feng X, Mu D, et al. Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition). Ann Transl Med [Internet]. 2020 Feb;8(3):47. Available from: http://www.ncbi.nlm.nih.gov/pubmed/32154287
http://www.ncbi.nlm.nih.gov/pubmed/32154... ). Although this expert working group has suggested breastfeeding only in cases of negative tests for SARS-CoV-2, this warning may contribute to reducing breastfeeding by women with no exposure to the virus which may lead to infant poor health outcomes. On the other hand, interim guidance provided by the Centers for Disease Control and Prevention (CDC) (¹⁷17. Centers for Disease Control and Prevention. Centers for Disease Control and Prevention. Pregnancy & Breastfeeding [Internet]. 2020 [cited 2020 Mar 18]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/prepare/pregnancy-breastfeeding.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fspecific-groups%2Fpregnancy-faq.html#anchor_1584169714
https://www.cdc.gov/coronavirus/2019-nco... ) and the World Health Organization (WHO) (¹⁸18. World Health Organization. Home care for patients with COVID-19 presenting with mild symptoms and management of their contacts. Interim guidance [Internet]. 2020 [cited 2020 Mar 17]. p. 1-4. Available from: https://www.who.int/publications-detail/home-care-for-patients-with-suspected-novel-coronavirus-(ncov)-infection-presenting-with-mild-symptoms-and-management-of-contacts
https://www.who.int/publications-detail/... ) advises that breastfeeding should be determined by the mother in coordination with her family and healthcare providers, and all possible prevention measures to avoid spreading the virus to the infant must be taken including wearing a mask and washing hands and breasts with soap and water before breastfeeding. If the woman opts to express breast milk, all recommendations for cleaning the breast pumps and utensils after each use must be rigorously followed. Consideration should be given to the possibility of someone healthy providing breast milk to the infant using a cup or spoon. This person must receive training from a qualified professional before starting procedures. If there is no production of breast milk by the mother, a human milk bank should be contacted. There are no restrictions on the use of milk from a human breast milk bank (¹⁹19. Center for Disease Control and Prevention (CDC). Interim Considerations for Infection Prevention and Control of Coronavirus Disease 2019 (COVID-19) in Inpatient Obstetric Healthcare Settings [Internet]. Available from: https://www.cdc.gov/coronavirus/2019-ncov/hcp/inpatient-obstetric-healthcare-guidance.html
https://www.cdc.gov/coronavirus/2019-nco... ,²⁰20. Royal College of Obstetricians and Gynaecologists. Coronavirus (COVID-19) Infection in Pregnancy. Information for healthcare professionals. Version 1: Published Monday 9 March, 2020 [Internet]. Available from: https://www.rcog.org.uk/globalassets/documents/guidelines/coronavirus-co
https://www.rcog.org.uk/globalassets/doc... ). The possibility of drug excretion into breast milk with potential adverse effects in breastfeed neonates should also be analyzed (²¹21. Anderson PO. Breastfeeding and Respiratory Antivirals: Coronavirus and Influenza. Breastfeed Med [Internet]. 2020 Mar 1;15(3):128-128. Available from: https://www.liebertpub.com/doi/10.1089/bfm.2020.29149.poa
https://www.liebertpub.com/doi/10.1089/b... ). To date, there is no evidence on the presence of SARS-CoV-2 in breast milk of pregnant women with COVID-19. Data provided on current literature are still limited and breastfeeding of women with COVID-19 remains a controversial issue. Further studies with large samples are needed to confirm these results particularly given the importance of breastfeeding in preventing other childhood illnesses.

Author contributions.

All authors conceived the original idea and contributed to the analysis and interpretation of the results. All authors reviewed and approved the final version.

Disclaimer.

Authors hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the RPSP/PAJPH or the Pan American Health Organization (PAHO).

REFERENCES

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