key: cord-0970805-y1d2y9c0
authors: Yan, Jie; Guo, Juanjuan; Fan, Cuifang; Juan, Juan; Yu, Xuechen; Li, Jiafu; Feng, Ling; Li, Chunyan; Chen, Huijun; Qiao, Yuan; Lei, Di; Wang, Chen; Xiong, Guoping; Xiao, Fengyi; He, Wencong; Pang, Qiumei; Hu, Xiaoling; Wang, Suqing; Chen, Dunjin; Zhang, Yuanzhen; Poon, Liona C.; Yang, Huixia
title: Coronavirus disease 2019 (COVID-19) in pregnant women: A report based on 116 cases
date: 2020-04-23
journal: Am J Obstet Gynecol
DOI: 10.1016/j.ajog.2020.04.014
sha: 61c1d770ba265b60419acbdfe8dd25ceb2ec122f
doc_id: 970805
cord_uid: y1d2y9c0

Abstract Background The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health emergency. Data on the effect of COVID-19 in pregnancy are limited to small case series. Objectives To evaluate the clinical characteristics and outcomes in pregnancy and the vertical transmission potential of SARS-CoV-2 infection. Study Desigh Clinical records were retrospectively reviewed for 116 pregnant women with COVID-19 pneumonia from 25 hospitals in China between January 20 and March 24, 2020. Evidence of vertical transmission was assessed by testing for SARS-CoV-2 in amniotic fluid, cord blood, and neonatal pharyngeal swab samples. Results The median gestational age on admission was 38+0 (IQR 36+0-39+1) weeks. The most common symptoms were fever (50.9%, 59/116) and cough (28.4%, 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal radiologic findings were found in 96.3% (104/108) of cases. There were eight cases (6.9%, 8/116) of severe pneumonia but no maternal deaths. One of eight patients (1/8) that presented in the first- and early-second-trimester had a missed spontaneous abortion. Twenty-one of 99 patients (21.2%, 21/99) that had delivered had preterm birth, including six with preterm premature ruptured of membranes. The rate of spontaneous preterm birth before 37 weeks was 6.1% (6/99). There was one case of severe neonatal asphyxia that resulted in neonatal death. Eighty-six of the 100 neonates that had testing for SARS-CoV-2 had negative results, of these ten neonates had paired amniotic fluid and cord blood samples that were tested negative for SARS-CoV-2. Conclusions SARS-CoV-2 infection during pregnancy is not associated with an increased risk of spontaneous abortion and spontaneous preterm birth. There is no evidence of vertical transmission of SARS-CoV-2 infection when the infection manifests during the third-trimester of pregnancy.

C. What does this study add to what is already known? 90 SARS-CoV-2 infection during pregnancy is not associated with an 91 increased risk of spontaneous abortion and spontaneous preterm birth. 92

There is no evidence of vertical transmission of SARS-CoV-2 infection 93 when the infection manifests during the third-trimester of pregnancy. 94 95 33/116); 23.3% (27/116) patients presented without symptoms. Abnormal 117 radiologic findings were found in 96.3% (104/108) of cases. There were eight 118 cases (6.9%, 8/116) of severe pneumonia but no maternal deaths. One of 119 eight patients (1/8) that presented in the first-and early-second-trimester had 120 a missed spontaneous abortion. Twenty-one of 99 patients (21.2%, 21/99) 121 that had delivered had preterm birth, including six with preterm premature 122 ruptured of membranes. The rate of spontaneous preterm birth before 37 123 weeks was 6.1% (6/99). There was one case of severe neonatal asphyxia that 124 resulted in neonatal death. Eighty-six of the 100 neonates that had testing for 125 SARS-CoV-2 had negative results, of these ten neonates had paired amniotic 126 fluid and cord blood samples that were tested negative for SARS-CoV-2. 127

The coronavirus disease 2019 , caused by severe acute 143 respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health 144 emergency. Since the first case of COVID-19 pneumonia was reported in 145 and Middle East respiratory syndrome coronavirus (MERS-CoV), have 151 caused more than 10 000 cumulative cases in the past two decades, with 152 mortality rates of 10% for SARS-CoV and 37% for MERS-CoV. 5-9 SARS-CoV-153 2 belongs to the same β-coronavirus subgroup and it has genome similarity of 154 about 80% and 50% with SARS-CoV and MERS-CoV, respectively. 10 The 155 latest report from the World Health Organization (WHO) on March 3 rd , 11 156 estimated the global mortality rate of COVID-19 to be 3.4%; although recent Pregnant women are particularly susceptible to respiratory pathogens and 162 severe pneumonia, because of the physiologic changes in the immune and 163 cardiopulmonary systems (e.g. diaphragm elevation, increased oxygen 164 consumption, and edema of respiratory tract mucosa), which can render them 165 intolerant to hypoxia. The 1918 influenza pandemic caused a mortality rate of 166 2.6% in the overall population, but 37% among pregnant women. 13 In 2009, 167 pregnant women were reported to be at an increased risk for complications 168 from the pandemic H1N1 2009 influenza virus infection, with a higher 169 estimated rate of hospital admission than in the general population. 14 In 2003, 170 it was reported that around 50% of pregnant women who developed CoV were admitted to the intensive care unit (ICU), around 33% of pregnant 172 women with SARS-CoV required mechanical ventilation, and the mortality rate 173 was as high as 25% for these women. 15 174 175 To date, data on the effect of COVID-19 in pregnancy are limited to small 176 case series. [16] [17] [18] [19] [20] The objective of this multicenter study of 116 pregnant 177 women with COVID-19 pneumonia is to evaluate the clinical characteristics 178 and outcomes in pregnancy and the vertical transmission potential of SARS-

This study was reviewed and approved by the Medical Ethical Committee of 184 

Of the 116 pregnant women with COVID-19 pneumonia, eight cases 305 presented before 24 weeks. One case (12.5%, 1/8) was complicated with a 306 missed spontaneous abortion at 5 +2 weeks at presentation with fever and 307 fatigue. In the remaining seven ongoing cases, four had reached 20 weeks 308 and morphology scan showed normal anatomy and fetal growth. Ten cases 309 presented between 24 and 33 +6 weeks, of which seven cases are ongoing, 310 one delivered at term and two cases (20%, 2/10) had iatrogenic preterm 311 delivery. One had a Cesarean delivery at 28 +1 weeks on the same day of 312 admission for severe pneumonia; one had a Cesarean delivery at 31 +6 weeks 313 on the same day of admission for twin pregnancy. Cesarean delivery in 18.8% (16/85), fetal distress in 10.6% (9/85) and failure to progress in 5.9% (5/85) ( Table 3 ). The rates of preterm delivery before 34 330 weeks and 37 weeks were 2.0% (2/99) and 21.2% (21/99), respectively 331 (Table 3) . Among the 21 preterm deliveries, 28.6% (6/21) had PPROM and 332 two of which resulted in vaginal deliveries. There were no cases with 333 spontaneous onset of labor. The rate of spontaneous preterm birth before 37 334 weeks was therefore 6.1% (6/99). No cases of spontaneous preterm delivery 335 before 34 weeks were reported. 336 337 There were no cases of fetal deaths. Among 100 neonates, there was one 338 case of severe neonatal asphyxia. 47.0% (47/100) neonates were transferred 339 to NICU for further treatment (Table 3 ). There was one case of neonatal death. 340

The mother of this neonate developed severe pneumonia and septic shock 341 after admission and required ICU admission for invasive ventilation. The 342 neonate (male) was delivered at 35 +2 weeks by Cesarean section and severe 343 neonatal asphyxia was reported. He had 1-min, 5-min and 10-min Apgar 344 scores of 1,1 and 1, respectively. He was treated with invasive ventilation and 345 died within 2 hours of birth. As of March 24, 2020, 76.0% (76/100) neonates 86.0% (86/100) of neonates were tested for SARS-CoV-2 viral nucleic acid on 350 pharyngeal swab samples and the results were negative. Ten of these 86 351 neonates had paired amniotic fluid and cord blood samples that were tested 352 negative for SARS-CoV-2. 16 which is similar to the rate of severe disease that has been reported across 400

China. 28, 29 This finding can be attributed to our proactive and aggressive 401 management of diagnosed pregnant cases in order to minimize the risk of 402 disease progression. There was a lot of unknown at the beginning of the 403 COVID-19 outbreak and we could only base our practice on prior experience 404 with SARS-CoV. As we encountered more and more COVID-19 cases, we 405 adapted our management and care was provided by a multidisciplinary team 406 including obstetricians, intensivists, obstetric anesthetists, virologists, 407 microbiologists, neonatologists, and infectious-disease specialists. pandemic has reached a critical stage, we believe it is important to report our 462 pregnant cases in relation to the risk of spontaneous abortion, preterm birth 463 and vertical transmission, without waiting for complete outcome data to be 464

available. This will delay this publication by several months. Second, we 465 included cases that were diagnosed based on clinical criteria in this series. 466

According to the WHO, these cases would have been classified as probable 467 cases of COVID-19 pneumonia. Given all clinically diagnosed cases had 468 patchy shadowing or ground-glass opacity on chest CT and significant 469 epidemiological exposure, we believed it was important to include these cases Normal range in pregnancy: first-trimester 5.7-13.6 x10 9 /L, second-trimester 5.6-14.8 x10 9 /L, and third-trimester 5.9-16.9 x10 9 /L (from Williams Obstetrics 25 th Edition 27 ). Data are n (%). Increased means over the upper limit of the normal range and decreased means below the lower limit of the normal range. COVID-19:

coronavirus disease 2019, CT: Computed tomography. Apgar 1min, Median (IQR) 9 (8,9) 9 (8,9) 9 (9,9) Apgar 5min, Median (IQR) 10 (9,10) 10 (9,10) 10 (10,10)

Severe neonatal asphyxia, n (%) 1 (1.0) 1 (2.0) 0 1,1 9,10 9,10 8,9 10,10 10,10 9,10 8,9

Neonatal asphyxia + -------Transferred to NICU + -- 

Management of first-trimester 615 miscarriage: a systematic review and network meta-analysis

Antibodies in Infants Born to Mothers With 618

COVID-19 Pneumonia

Possible Vertical Transmission of SARS-620

CoV-2 From an Infected Mother to Her Newborn