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Table 1.  Maternal Characteristics, Clinical Presentation, and Obstetrical Management
Maternal Characteristics, Clinical Presentation, and Obstetrical Management
Table 2.  Maternal and Neonatal Outcomesa
Maternal and Neonatal Outcomesa
1.
Chen  L, Li  Q, Zheng  D,  et al.  Clinical characteristics of pregnant women with Covid-19 in Wuhan, China.   N Engl J Med. Published online April 17, 2020. doi:10.1056/NEJMc2009226PubMedGoogle Scholar
2.
Della Gatta  AN, Rizzo  R, Pilu  G, Simonazzi  G.  Coronavirus disease 2019 during pregnancy: a systematic review of reported cases.   Am J Obstet Gynecol. Published online April 18, 2020. doi:10.1016/j.ajog.2020.04.013PubMedGoogle Scholar
3.
Kimberlin  DW, Stagno  S.  Can SARS-CoV-2 infection be acquired in utero? more definitive evidence is needed.   JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4868PubMedGoogle Scholar
4.
Middleton  PG, Gade  EJ, Aguilera  C,  et al.  ERS/TSANZ Task Force statement on the management of reproduction and pregnancy in women with airways diseases.   Eur Respir J. 2020;55(2):1901208. doi:10.1183/13993003.01208-2019PubMedGoogle Scholar
5.
Sandall  J, Tribe  RM, Avery  L,  et al.  Short-term and long-term effects of caesarean section on the health of women and children.   Lancet. 2018;392(10155):1349-1357. doi:10.1016/S0140-6736(18)31930-5PubMedGoogle ScholarCrossref
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    1 Comment for this article
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    Could Cesarean Delivery Reduce the Infection Risks of COVID-19 for the Newborns?
    Ruihong Xue, M.D. Obst. and Gyn. | International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
    We read with interest the article by Oscar Martínez-Perez and colleagues entitled "Association Between Mode of Delivery Among Pregnant Women With COVID-19 and Maternal and Neonatal Outcomes in Spain". We would like to discuss some points that merit further consideration.

    In the article, the authors divided patients infected with COVID-19 into three groups based on degree of severity. Different pregnancy and neonatal outcomes were compared and conducted with statistical methods among these groups. They found that cesarean birth was statistically significantly associated with worse outcomes, especially ICU admission.

    Despite the limitations of the study, especially the small sample
    of patients, this study provide important messages for the selection of mode of deliveries among those who have been infected with COVID-19, which indicated that Cesarean birth was not better than vaginal delivery on outcomes.

    However, as we all know, COVID-19 is a highly contagious respiratory virus. Vaginal birth usually takes longer than cesarean delivery, which might increase the risks of infection of COVID-19 during the second stage.

    Until now there is no evidence whether Cesarean delivery would reduce the infection risks of COVID-19 for newborns. All in all, more research should be performed to provide evidence from a clinical perspective.

    CONFLICT OF INTEREST: None
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    Research Letter
    June 8, 2020

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

    Author Affiliations
    • 1Obstetrics and Gynaecology Department, Puerta de Hierro University Hospital, Madrid, Spain
    • 2Department Woman-Mother-Child, Lausanne University Hospital, Lausanne, Switzerland
    • 3Obstetrics and Gynaecology Department, 12 Octubre University Hospital, Madrid, Spain
    • 4Service of Pharmacy, Lausanne University Hospital, Lausanne, Switzerland
    • 5Obstetrics and Gynaecology Department, Gregorio Marañon University Hospital, Madrid, Spain
    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.

    Methods

    Women with singleton pregnancies and a positive reverse transcriptase–polymerase chain reaction (RT-PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between March 12 and April 6, 2020, and who delivered within the next 14 days at 96 level 2 or level 3 maternity hospitals throughout Spain were included.

    The study was approved by the national ethics committee. Oral informed consent was obtained.

    Pregnant women were tested if they presented with symptoms compatible with COVID-19 or a history of potential exposure; additionally, universal screening was started in some hospitals in April. Newborns had a nasopharyngeal swab obtained for RT-PCR within 6 hours of life.

    Mothers were stratified by symptom severity at admission as asymptomatic, mild, or severe (need for advanced oxygen support: high-flow nasal cannula, noninvasive ventilation, or mechanical ventilation).

    Maternal outcomes were defined as severe if mothers required advanced oxygen support or admission to the intensive care unit (ICU) or had signs of sepsis with hypoperfusion/organ dysfunction. Clinical deterioration was defined by an increased need for oxygen supplementation after delivery.

    Neonatal outcomes considered were neonatal ICU (NICU) admission and rates of SARS-CoV-2 perinatal transmission.

    Multivariable logistic regression was performed assessing the association between mode of delivery and maternal and neonatal outcomes among patients with mild symptoms, adjusting for maternal age, body mass index, comorbidities, need for oxygen supplementation at admission, abnormal chest x-ray findings at admission, nulliparity, smoking, and prematurity. Stata version 14 (StataCorp) was used. A 2-tailed P < .05 defined statistical significance.

    Results

    Of 82 pregnant patients included, 4 presented with severe COVID-19 symptoms, including 1 with concomitant preeclampsia; all 4 underwent cesarean delivery and required ICU admission.

    Seventy-eight patients presented with no or mild COVID-19 symptoms, including 11 patients requiring oxygen supplementation. Forty-one (53%) delivered vaginally and 37 (47%) by cesarean delivery, 29 for obstetrical indications and 8 for COVID-19 symptoms without other obstetrical indications. Women with cesarean deliveries were more likely to be multiparous, be obese, require oxygen at admission, and have abnormal chest x-ray findings than those delivering vaginally (Table 1). No patients with a vaginal delivery developed severe adverse outcomes, while 5 (13.5%) with cesarean delivery required ICU admission. Two patients (4.9%) with a vaginal delivery had clinical deterioration after birth vs 8 (21.6%) with cesarean delivery. After adjustment for potential confounding factors, cesarean birth was significantly associated with clinical deterioration (adjusted odds ratio, 13.4; 95% CI, 1.5-121.9; P = .02) (Table 2).

    Eight newborns (19.5%) delivered vaginally and 11 (29.7%) born by cesarean delivery were admitted to the NICU. After adjustment for confounding factors, cesarean birth was significantly associated with an increased risk of NICU admission (adjusted odds ratio, 6.9; 95% CI, 1.3-37.1; P = .02).

    Three (4.2%) of 72 newborns tested within 6 hours after birth had a positive SARS-CoV-2 RT-PCR result. Repeat testing at 48 hours was negative. None developed COVID-19 symptoms within 10 days.

    Two other newborns, both cesarean deliveries at term, developed COVID-19 symptoms within 10 days. Though initial testing at birth was negative, repeat testing was positive. Both newborns were in contact with their parents immediately after birth. Symptoms resolved within 48 hours.

    Discussion

    In this cohort of pregnant women in Spain, severe adverse maternal outcomes occurred in 11% (9/82), 4 of whom presented with severe and 5 with mild COVID-19 symptoms.

    Among patients with mild symptoms at presentation, all patients with a vaginal birth had excellent outcomes. In contrast, 13.5% of women undergoing cesarean delivery had severe maternal outcomes and 21.6% had clinical deterioration. Women undergoing cesarean delivery may have been at higher risk of adverse outcomes, but after adjusting for confounding factors, cesarean birth remained independently associated with an increased risk of clinical deterioration. The physiological stress induced by surgery is known to increase postpartum maternal complications.4,5 Cesarean delivery was also associated with an increased risk of NICU admission.

    Limitations include a lack of sufficient information on newborns to determine vertical transmission. Also, the 95% CIs around the odds ratios for cesarean birth were wide and the estimates fragile.

    Section Editor: Jody W. Zylke, MD, Deputy Editor.
    Back to top
    Article Information

    Corresponding Author: David Baud, MD, PhD, Materno-Fetal and Obstetrics Research Unit, Department of Obstetrics and Gynecology, Centre Hospitalier Universitaire Vaudois, 1011 Lausanne, Switzerland (david.baud@chuv.ch).

    Accepted for Publication: May 26, 2020.

    Published Online: June 8, 2020. doi:10.1001/jama.2020.10125

    Author Contributions: Drs Martínez-Perez and Vouga had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Martínez-Perez and Vouga contributed equally.

    Concept and design: Martínez-Perez, Vouga, Cruz Melguizo, Panchaud.

    Acquisition, analysis, or interpretation of data: Martínez-Perez, Vouga, Forcen Acebal, Panchaud, Muñoz-Chápuli, Baud.

    Drafting of the manuscript: Vouga, Cruz Melguizo, Forcen Acebal, Panchaud, Baud.

    Critical revision of the manuscript for important intellectual content: Martínez-Perez, Vouga, Panchaud, Muñoz-Chápuli, Baud.

    Statistical analysis: Martínez-Perez, Vouga, Panchaud, Muñoz-Chápuli, Baud.

    Obtained funding: Martínez-Perez.

    Administrative, technical, or material support: Martínez-Perez, Cruz Melguizo, Muñoz-Chápuli, Baud.

    Supervision: Martínez-Perez, Cruz Melguizo, Panchaud, Muñoz-Chápuli, Baud.

    Conflict of Interest Disclosures: None reported.

    Additional Contributions: We thank the Emergencia Obstetrica España Group for participation in the study. We also thank Tirso Perez Medina, MD, PhD, Obstetrics and Gynaecology Department, Puerta de Hierro University Hospital, Autonoma University, Madrid, Spain, for his contribution to the design of the study and data collection. He received no compensation for his participation.

    References
    1.
    Chen  L, Li  Q, Zheng  D,  et al.  Clinical characteristics of pregnant women with Covid-19 in Wuhan, China.   N Engl J Med. Published online April 17, 2020. doi:10.1056/NEJMc2009226PubMedGoogle Scholar
    2.
    Della Gatta  AN, Rizzo  R, Pilu  G, Simonazzi  G.  Coronavirus disease 2019 during pregnancy: a systematic review of reported cases.   Am J Obstet Gynecol. Published online April 18, 2020. doi:10.1016/j.ajog.2020.04.013PubMedGoogle Scholar
    3.
    Kimberlin  DW, Stagno  S.  Can SARS-CoV-2 infection be acquired in utero? more definitive evidence is needed.   JAMA. Published online March 26, 2020. doi:10.1001/jama.2020.4868PubMedGoogle Scholar
    4.
    Middleton  PG, Gade  EJ, Aguilera  C,  et al.  ERS/TSANZ Task Force statement on the management of reproduction and pregnancy in women with airways diseases.   Eur Respir J. 2020;55(2):1901208. doi:10.1183/13993003.01208-2019PubMedGoogle Scholar
    5.
    Sandall  J, Tribe  RM, Avery  L,  et al.  Short-term and long-term effects of caesarean section on the health of women and children.   Lancet. 2018;392(10155):1349-1357. doi:10.1016/S0140-6736(18)31930-5PubMedGoogle ScholarCrossref
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