key: cord-0763273-sl0mq981
authors: Garcia-Ruiz, Itziar; Sulleiro, Elena; Serrano, Berta; Fernandez-Buhigas, Irene; Rodriguez-Gomez, Leire; Sanchez-Nieves, David; Anton-Pagarolas, Andrés; Esperalba-Esquerra, Juliana; Frick, Marie Antoinette; Camba, Fatima; Navarro-Jimenez, Alexandra; Fernandez-Hidalgo, Nuria; Maiz, Nerea; Carreras, Elena; Suy, Anna
title: Congenital infection of SARS-CoV-2 in live-born neonates: a population-based descriptive study
date: 2021-06-19
journal: Clin Microbiol Infect
DOI: 10.1016/j.cmi.2021.06.016
sha: 8477bd1451a4f3d84945df72bf635f10c3905e34
doc_id: 763273
cord_uid: sl0mq981

OBJECTIVE: This study aimed to evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). METHODS: This is a descriptive, multicenter, observational study in nine tertiary care hospitals throughout Spain. The study population was women with COVID-19 during pregnancy. Mother-to-child transmission was defined as positive real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. RESULTS: We included 43 singleton pregnant women and one twin pregnancy, thus we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14 to 41.3). The median interval between positive RT-PCR and delivery was 21.5 days (range 0 to 141 days). Fourteen women (31.8%, 95%CI 18.6-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95%CI 0.1-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95%CI 0-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95%CI 0.2-41.3%). CONCLUSIONS: The presence of the SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Methods. This is a descriptive, multicenter, observational study in nine tertiary 48 care hospitals throughout Spain. The study population was women with COVID-49 19 during pregnancy. Mother-to-child transmission was defined as positive real-50 time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) of SARS-CoV-51 2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs 52 taken immediately after birth. 53

Results. We included 43 singleton pregnant women and one twin pregnancy, 54 thus we obtained 45 samples of placenta, amniotic fluid and umbilical cord 55 blood. The median gestational age at diagnosis was 34.7 weeks (range 14 to 56 41.3). The median interval between positive RT-PCR and delivery was 21.5 57 days (range 0 to 141 days). Fourteen women (31.8%, 95%CI 18.6-47.6%) were 58 positive at the time of delivery. There was one singleton pregnancy with SARS-59

CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood 60 (2.2%, 95%CI 0.1-11.8%). Nasopharyngeal aspiration was performed on 38 61

neonates at birth, all of which were negative (0%, 95%CI 0-9.3%). In 11 62 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one 63 returned positive (9.1%, 95%CI 0.2-41.3%). if the symptoms started in the last seven days the RT-PCR was repeated after 100 24 hours, otherwise a serology test was performed. 101 102

The primary outcome was evidence of mother-to-child transmission, defined as 104 positive RT-PCR of SARS-CoV-2 in amniotic fluid, cord blood, placenta or 105 neonatal nasopharyngeal swabs taken immediately after birth [7] . 106 previous 14 days, physical examination, laboratory and radiologic findings were 110 collected. COVID-19 severity was classified into three groups: mild (not 111 requiring hospital admission), severe (pneumonia), and critical (ICU admission). 112 Data on pregnancy, gestational age at delivery, mode of delivery, indication for 113 cesarean delivery, maternal complications and neonatal outcomes were also 114 recorded. Other studies (4-6, 8-11) may only consider possible or even unlikely congenital 169 infection because there are not enough specimens from the mother or the 170 newborn and contamination during labour or caesarean cannot be ruled out. 171

Our newborn nasopharyngeal RT-PCR was negative. In Vivanti´s case, 172 neonatal respiratory sample was obtained from non-bronchoscopic 173 bronchoalveolar lavage before extubation, which is more sensitive [15] . Testing 174 RT-PCR in other tissues may improve the detection of the virus in neonates. 175

However, maternal origin postnatally or cross-reactivity with nonspecific 178 antibodies can never be excluded entirely. 179

The sample size is small. Due to the epidemiological time when the patients 180 were recruited, personal protective equipment was lacking, and ethics approval 181 was substantially delayed, making samples collection challenging. Besides, in 182 some cases, amniocentesis was not possible due to premature rupture of 183

The findings of this study support the possibility of mother-to-child transmission, 185 even it seems to be rare. A larger cohort would be necessary to accurately 186 evaluate the rate of congenital transmission and assess the newborn's potential 187 consequences. 

Coronavirus disease 2019 in pregnant 213 women: a report based on 116 cases

Clinical 216 manifestations, risk factors, and maternal and perinatal outcomes of coronavirus 217 disease 2019 in pregnancy: living systematic review and meta-analysis

Update: 220 Characteristics of Symptomatic Women of Reproductive Age with Laboratory-221

Confirmed SARS-CoV-2 Infection by Pregnancy Status -United States

Characteristics 225 and outcomes of pregnant women admitted to hospital with confirmed SARS-226

CoV-2 infection in UK: national population based cohort study

Association Between Mode of Delivery Among Pregnant 230 2020

CoV-2 vertical transmission during pregnancy

Classification system and 263 case definition for SARS-CoV-2 infection in pregnant women, fetuses, and 264 neonates

Laboratory diagnosis of emerging human coronavirus 267 infections-the state of the art