key: cord-0735983-zlvfdb2j authors: Parazzini, Fabio; Bortolus, Renata; Mauri, Paola Agnese; Favilli, Alessandro; Gerli, Sandro; Ferrazzi, Enrico title: Delivery in pregnant women infected with SARS‐CoV‐2: A fast review date: 2020-05-01 journal: Int J Gynaecol Obstet DOI: 10.1002/ijgo.13166 sha: ce1faf8dafa1bc89cbf1e8c260612e9cd97b4aa0 doc_id: 735983 cord_uid: zlvfdb2j BACKGROUND: Few case reports and clinical series exist on pregnant women infected with SARS‐CoV‐2 who delivered. OBJECTIVE: To review the available information on mode of delivery, vertical/peripartum transmission, and neonatal outcome in pregnant women infected with SARS‐CoV‐2. SEARCH STRATEGY: Combination of the following key words: COVID‐19, SARS‐CoV‐2, and pregnancy in Embase and PubMed databases. SELECTION CRITERIA: Papers reporting cases of women infected with SARS‐CoV‐2 who delivered. DATA COLLECTION AND ANALYSIS: The following was extracted: author; country; number of women; study design; gestational age at delivery; selected clinical maternal data; mode of delivery; selected neonatal outcomes. MAIN RESULTS: In the 13 studies included, vaginal delivery was reported in 6 cases (9.4%; 95% CI, 3.5–19.3). Indication for cesarean delivery was worsening of maternal conditions in 31 cases (48.4%; 95% CI, 35.8–61.3). Two newborns testing positive for SARS‐CoV‐2 by real‐time RT‐PCR assay were reported. In three neonates, SARS‐CoV‐2 IgG and IgM levels were elevated but the RT‐PCR test was negative. CONCLUSIONS: The rate of vertical or peripartum transmission of SARS‐CoV‐2 is low, if any, for cesarean delivery; no data are available for vaginal delivery. Low frequency of spontaneous preterm birth and general favorable immediate neonatal outcome are reassuring. The aim of the present article was to review the available information with special focus on mode of delivery, vertical/peripartum transmission, and immediate neonatal outcome of pregnant women infected with SARS-CoV-2. We searched PubMed (National Library of Medicine, Washington, DC) and Embase (Elsevier) databases from January 1 up to March 31, 2020, using a combination of the following key words: COVID-19, SARS-CoV-2, and pregnancy. We also reviewed the reference lists of retrieved articles to search for other pertinent studies. Two authors (FP and RB) reviewed the papers and independently selected the articles eligible for systematic review. Studies were selected if they met the following criteria: clinical studies, studies reporting original data, studies reporting SARS-CoV-2 infected women who delivered. A PICOS (Patient, Intervention, Comparator, Outcome, Study) design structure was used to develop the study questions and the inclusion/ exclusion criteria. The question was: "What is the mode of delivery and the obstetric and immediate neonatal outcomes in SARS-CoV-2 infected pregnant women?" (Table 1) . For each study, the following information was extracted: first author's last name; year; country; number of women who delivered; study design; gestational age at delivery; selected clinical maternal data (maternal age, comorbidity, diagnosis of pneumonia, treatment); mode of delivery; selected neonatal outcomes (birthweight, 5-minute Apgar score, admission to neonatal intensive care unit [NICU] neonatal diseases; SARS-CoV-2 positivity). The primary outcomes assessed were frequency of preterm birth (<37 weeks of gestation), vaginal delivery, Apgar score at 5 minutes <7, and newborn infection. For each study with binary outcomes, we calculated the 95% confidence intervals (CIs) of the estimated proportion. The initial search retrieved 41 abstracts from PubMed and 23 from Embase. After exclusion of unrelated abstracts of review papers, guidelines, and commentaries, 17 papers were selected for extensive review. Two studies reported data only on maternal outcome. 7, 8 Another paper was published without peer review. 9 One study was published in Chinese. 10 Therefore, a total of 13 studies were included. [4] [5] [6] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] Table 2 presents their main methodological characteristics. Six studies were case reports and seven were retrospective clinical series. A total of 64 pregnant women who delivered were reported in the studies (seven women admitted to hospital but who did not deliver at the time of publication were also reported). 19 are not included since the indication for cesarean section was unclear in the text. Preterm birth (<37 weeks of gestation) was observed in 19 cases among the 48 for which the information on gestational age at delivery was available (39.6%; 95% CI, 25.8-54.7). In only two cases, reported by Zhu et al., 5 delivery was due to spontaneous preterm labor (1 twin pregnancy and 1 premature rupture of membranes). Table 5 presents data on the immediate neonatal outcome and the frequency of SARS-Cov-2 positivity in the newborns. Low birthweight (<2500 g) was observed in 10 newborns (10/37 [27.0%] for which information was available; 95% CI, 13.8-44.1). In all cases, 5-minute Apgar score was greater than 7. One neonatal death due to disseminated intravascular coagulation (DIC) syndrome was reported. The death occurred in a singleton male neonate born by cesarean delivery at 34 + 5 weeks of gestation and weighing 2200 g. The cause of death was multiple organ failure and DIC. Considering respiratory disease in newborns, one case of pneumonia, one low-grade fever and haziness in both lung fields, one high-density nodular shadow under the pleura of the right lung, six shortness of breath, and two cases of neonatal respiratory distress syndrome were reported. Wang et al. 16 reported a case of neonatal COVID-19 infection with pharyngeal swabs testing positive by rRT-PCR assay 36 hours after cesarean delivery; whether the case is a vertical transmission from mother to child remains to be confirmed. Finally, Yu et al. 17 reported the case of a RT-PCR positive test in a newborn 36 hours after cesarean birth. The results of this fast review of the available data on mode of delivery and immediate neonatal outcome in pregnant women infected with SARS-CoV-2 suggest that the risk of vertical or peripartum transmission of the virus to the newborn is limited, if any. T A B L E 2 Study characteristics and sample size of the studies included in the review. T A B L E 3 Maternal characteristics and clinical conditions of the women in the included studies. Chen et al. 4 26-40 2 GH/9 6/9 9/9 9/9 0 a /9 Chen et al. 20 IgM antibodies to SARS-CoV-2 were found in three cases. 11, 19 Caution in interpreting these findings has been suggested, including the possibility that IgM positivity could represent a laboratory artifact. 23 These findings suggest that transmission in utero is possible. However, SARS-CoV-2 was not found in amniotic fluid or cord blood and this finding is based on very few cases. ing. 24 The risk of ingestion or aspiration of cervicovaginal secretions or contact with perineal infected tissue is higher with vaginal delivery. In this review we identified 19 women who delivered preterm, although spontaneous vaginal preterm birth was reported in only two cases. Therefore, there is reassuring evidence that COVID-19 infection of the mother did not markedly increase the risk of spontaneous preterm birth. Regarding maternal conditions, we note that COVID-19 infection in pregnancy seems to be less severe than other coronavirus infections such as SARS or MERS. 2, 3 We identified two women who needed intensive care. The proportion of women requiring CCU admission seems to be similar to that reported in the general population affected by COVID-19. 25 However, worsening of maternal condition was the cause of emergency cesarean delivery in about 45% of women. Diabetes and hypertension are considered determinants of worse prognosis in cases of infection. 25 However, we were unable to analyze this in detail; the few cases reported with diabetes did not need CCU admission. Finally, newborn outcome deserves some consideration. In all reported cases the 5-minute Apgar score was greater than 7 and generally 9 or 10 (data not shown in table). Furthermore, the frequency of NICU admission was low and due to medically induced preterm birth. However, one neonatal death and several cases of respiratory symptoms or diseases were reported by pharyngeal or nasopharyngeal swabs, although these tested negative for SARS-CoV-2 by rRT-PCR assay, except in one case. 16 Very few reported cases provided information on the risk of newborn infection during breastfeeding. Guidelines suggest allowing breastfeeding for infected women who wear a mask. 26 FP and EF designed the study. FP and RB reviewed the identified papers. FP and RB drafted the manuscript. PM, SG, AF and EF revised the manuscript. All authors reviewed and approved the final manuscript. The authors have no conflicts of interest. 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