Screening of severe acute respiratory syndrome coronavirus-2 infection during labor and delivery using polymerase chain reaction and immunoglobulin testing

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Sc eening o se e e acu e espi a o y synd ome co ona i us-2 in ec ion du ing labo and deli e y using polyme ase chain eac ion and immunoglobulin es ing Rica do Sa i ´ on-Co nudella a , * , Ana Villalba a , Luis M. Es eban b , Mau icio Tajada c , Bel´ en Rod íguez-Solanilla c , Me cedes Andey o-Ga cia a , Ja ie Zapa diel d , Segundo Ri e e , Be a Cas ´ an-La az , Faus ino R. P´ e ez-L´ opez g a Depa men o Obs e ics and Gynecology, Villalba Gene al Uni e si y Hospi al, Mad id, Spain b Escuela Uni e si a ia Poli ´ ecnica de La Almunia, Uni e sidad de Za agoza, Za agoza, Spain c Depa men o Obs e ics and Gynecology, Miguel Se e Uni e si y Hospi al, Za agoza, Spain d Depa men o Mic obiology, Villalba Gene al Uni e si y Hospi al, Mad id, Spain e Neona ology Uni , Miguel Se e Uni e si y Hospi al, Za agoza, Spain Depa men o Obs e ics and Gynecology, San Ped o Hospi al, Log o˜ no, Spain g A agon Heal h Resea ch Ins i u e, and Depa men o Obs e ics and Gynecology, Uni e si y o Za agoza Facul y o Medicine, Za agoza, Spain ARTICLE INFO Keywo ds: Co ona i us 2019 COVID-19 Labo and deli e y Polyme ase chain eac ion SARS-CoV-2 Se um immunoglobulins ABSTRACT Aims: To assess se e e acu e espi a o y synd ome co ona i us-2 (SARS-CoV-2) in ec ion du ing labo and de- li e y wi h polyme ase chain eac ion (PCR) and using immunoglobulin G and M es ing o co ela e wi h ma e nal and pe ina al ou comes. Main me hods: P egnan women admi ed o labo and deli e y a wo Spanish hospi als we e sc eened o SARS- CoV-2 in ec ion by PCR es and by de ec ion o se um immunoglobulins G and M. Ma e nal and pe ina al ou comes we e compa ed in women wi h labo a o y e idence o SARS-CoV-2 in ec ion wi h hose wi h nega i e es s. Key indings: Be ween Ma ch 31s and Sep embe 30 h, 2020, 1211 p egnan women we e sc eened o SARS- CoV-2 in ec ion. The p e alence o labo a o y e idence o SARS-CoV-2 in ec ions was 5.4% (n =65), co e- sponding o (i) 22 ongoing in ec ions a admission, including wo wi h mild clinical symp oms and 20 asymp- oma ic women; (ii) 43 cases o p e ious SARS-CoV-2 exposu e; (iii) and 1146 women who we e nega i e o bo h SARS-CoV-2 PCR and se ological es . None o he sc eened mo he s equi ed hospi al admission o co ona i us disease be o e o a e deli e y, no we e any o he newbo ns admi ed o he in ensi e ca e uni . All newbo ns om mo he s wi h posi i e PCR on admission we e PCR nega i e. The e we e no signi ican di e - ences in ma e nal o pe ina al ou comes among he h ee s udied g oups. Signi icance: Ongoing o p e ious SARS-CoV-2 in ec ion wi h asymp oma ic o mild clinical symp oms de ec ed du ing sc eening in p egnan women a labo and deli e y do no ha e a highe a e o ad e se ma e nal o pe ina al ou comes. 1. In oduc ion Se e e acu e espi a o y synd ome co ona i us 2 (SARS-CoV-2) is esponsible o he mos apid epidemic in he his o y o humankind. A he end o Decembe 2020, he Wo ld Heal h O ganiza ion epo ed o e 79.2 million cases and o e 1.7 million dea hs since he s a o he pandemic [1]. In p egnan women he i al in ec ion has been associa ed wi h ad e se ou comes [2] and he isk o e ical ans- mission is a ma e o deba e [3,4]. The i s epo ed cases o his in ec ion in p egnan women om Wuhan (China) p esen ed wi h pneumonia, con i med by ches compu ed omog aphy. They we e ea ed be ween Decembe 2019 and Ma ch 2020, and p esen ed a posi i e polyme ase chain eac ion (PCR) [5]. Howe e , a la ge p o- po ion o p egnan women had less se e e o asymp oma ic o ms o he * Co esponding au ho a : Camino de Mo alza zal M-608 Km, Calle Alped e e 41, 28400 Collado Villalba, Mad id, Spain. E-mail add esses: [email p o ec ed], [email p o ec ed] (R. Sa i ´ on-Co nudella). Con en s lis s a ailable a ScienceDi ec Li e Sciences jou nal homepage: www.else ie .com/loca e/li escie h ps://doi.o g/10.1016/j.l s.2021.119200 Recei ed 7 Decembe 2020; Recei ed in e ised o m 1 Feb ua y 2021; Accep ed 3 Feb ua y 2021 Li e Sciences 271 (2021) 119200 2 in ec ion du ing he same pe iod. The e iew o Pe i osso e al. [6] p o ided in o ma ion om 1287 con i med in ec ions in p egnan women, including 19 in ec ed neona es. When uni e sal sc eening is unde aken, he ma e nal asymp oma ic in ec ion a es ange om 43.5 o 92% o cases. I seems ha he a iable numbe o se e e clinical cases in g a ids could be ela ed o di e ences in i al p e alence among hei espec i e communi ies. The sys ema ic e iew by Hun ley e al. [7] o 13 s udies (including a leas 10 p egnan women wi h SARS-CoV-2 in ec ion) poin ed ou he low a e o se e e cases, epo ing in ensi e ca e uni admission a 3.0%, ma e nal c i ical disease a 1.4%, and no ma e nal dea hs. Howe e , p e e m bi h and cesa ean deli e y a es a e inc eased and in luenced by di e en c i ical p ac ices. The ecen me a-analysis by Yee e al. [8] concluded ha du ing p egnancy, SARS-CoV-2 in ec ion displays ela- i ely mild symp oms, mo e equen labo a o y pa ame e al e a ions han in non-p egnan women, a e al SARS-CoV-2 a ec ion o a ound 2%, and a neona al dea h a e o 0.4%. Howe e , new ala ming da a ha e been epo ed om mac o-s udies on he se e i y o he SARS-CoV- 2 in ec ion and mo ali y in p egnan women, such as he Mexican Na- ional s udy [9,10]. SARS-CoV-2 sc eening o p egnan women du ing labo and deli e y has been a widesp ead clinical p ac ice since he beginning o he pandemic [11,12]. The p e alence o SARS-CoV-2 among his popula- ion anges om 0.43 o 19.9%, depending on he poin along he pandemic cu e ( i s wa e, second wa e, o in e wa e pe iod), and whe e he s udy was ca ied ou [12–15]. In compa ison o non- p egnan adul s, hal o g a ids wi h SARS-CoV-2 pneumonia display a no mal ini ial body empe a u e wi h leukocy osis and lymphopenia. Mo eo e , mixed consolida ion and comple e consolida ion we e com- mon among labo a o y-con i med cases [3]. High asymp oma ic a es (43–88%) ha e also been demons a ed among p egnan women admi ed o labo and deli e y [11,14–17], esembling a es in he non- p egnan popula ion (86%) [18]. The main diagnos ic ool o he de ec ion o ongoing in ec ion wi h SARS-CoV-2 has been polyme ase chain eac ion (PCR). S udies ha e p oposed he sc eening o SARS-CoV-2 o p egnan women du ing labo and deli e y, including bo h he PCR and plasma enzyme-linked immunoso ben assay (ELISA) plasma SARS-CoV-2 G and M immunoglobulin (Ig) es ing [19,20]. This app oach has been pos u- la ed o p o ide a much mo e accu a e p e alence han PCR alone. The main objec i e o he p esen s udy was o assess he alue o combined PCR and IgG and M de ec ion by se ological es s pe o med du ing labo and deli e y, and o co ela e esul s wi h ad e se ma e nal (AMOs) and pe ina al (APOs) ou comes in h ee g oups o p egnan women: (i) ongoing SARS-CoV-2 in ec ion (posi i e PCR), (ii) p e ious i al in ec- ion (nega i e PCR wi h posi i e IgG ega dless o IgM), and (iii) no e idence o in ec ion (asymp oma ic woman wi h bo h nega i e PCR and nega i e IgM and IgG es s). 2. Me hods This coho s udy was conduc ed be ween he 31s o Ma ch and 31s o Sep embe 2020, a he Villalba Gene al Uni e si y Hospi al, Mad id, and he Miguel Se e Uni e si y Hospi al, Za agoza, Spain. The esea ch p o ocol was app o ed by he Fundaci´ on Jim´ enez Díaz Clinical Resea ch E hics Commi ee, Mad id, Spain (P o ocol EO194-20_HGV), and he Clinical Resea ch E hics Commi ee o A agon (PI 20/508). The STROBE s a emen o obse a ional s udies was ollowed du ing s udy [21]. A o al o 1211 p egnan women admi ed o labo and deli e y o scheduled o labo induc ion o cesa ean deli e y we e sc eened by PCR using nasopha yngeal swabs and es ing IgG and IgM class an ibodies. The inclusion c i e ion conside ed p egnancies o e 23 weeks in ges a- ions wi h spon aneous o induced labo . Exclusion c i e ia co e- sponded o non-p egnan women, win p egnancies, and neona al o in au e ine dea hs due o e al mal o ma ions. Th ee pa ien s wi h nega i e PCR, posi i e IgM and nega i e IgG we e conside ed as possible alse-posi i e cases and we e excluded ollowing he ecommenda ions o he Spanish Minis y o Heal h Guidelines [22]. We eco ded he ollowing ma e nal cha ac e is ics: age, pa i y, hype ensi e diso de s, and p eges a ional and ges a ional diabe es melli us. Ad e se ma e nal ou comes included in apa um e e , and hemo hage o pos pa um u e ine a ony. O he symp oms such as cough, hino hea, dyspnea, ches pain, dia hea, myalgia, new anosmia, o ageusia we e eco ded, bu wi h no incidence. Obs e ic and pe ina al da a eco ded o each deli e y co esponded o newbo n sex, deli e y ( aginal, ins umen al, o cesa ean deli e y), ges a ional age a bi h, bi h weigh , pe cen ile o he bi h weigh , and a e ial co d blood pH. We also eco ded he ollowing ad e se pe ina al ou comes: small o ges a ional age (bi h weigh less han 3 d pe cen ile), 5 min Apga sco e <7, a e ial co d blood <7.10, ins umen al deli e y o non- eassu ing e al s a us (NRFS), cesa ean deli e y o NRFS, s ill- bi h, and neona al In ensi e Ca e Uni (ICU) admission a es. All he women we e classi ied in o one o he h ee SARS-CoV-2 ca ego ies: (i) ongoing in ec ion (posi i e PCR); (ii) p e ious in ec ion (nega i e PCR wi h posi i e IgG ega dless o IgM), ollowing he ec- ommenda ions o he Spanish Minis y o Heal h Guidelines [12]; and (iii) women wi h no e idence o SARS-CoV-2 in ec ion (nega i e PCR and nega i e IgG and IgM es s). 2.1. Labo a o y es s A he Villalba Gene al Uni e si y Hospi al, ELISA se ological IgG and IgM es ing we e ca ied ou in p egnan women wi h posi i e PCR o posi i e apid an ibody es . The apid an ibody es is a la e al low immunoch oma og aphic assay ha uses he Biozek co ona i us 2019 IgG/IgM Rapid Tes Casse e. The ELISA se ological p esence o an i- bodies was de e mined o G ype wi h Abbo eagen , and o M ype wi h Vi cell eagen . A he Miguel Se e Uni e si y Hospi al, PCR e- agen s co esponded o he Xpe Xp ess SARS-CoV-2, Liaison® SARS- CoV-2 solu ions, and he Viasu e SARS-CoV-2 eal- ime PCR de ec ion ki . The ELISA se ological p esence o IgM and IgG was de e mined using he Liaison Diaso in eagen . 2.2. S a is ical analysis As con inuous a iables did no ollow a no mal dis ibu ion, median and in e qua ile anges we e calcula ed, and o ca ego ical a iables, absolu e o ela i e equencies we e epo ed. Compa isons among he h ee SARS-CoV-2 pa ien ca ego ies (ongoing in ec ion, p e ious in ec ion, and women wi h no e idence o ongoing o p e ious SARS- CoV-2 in ec ion) we e pe o med by K uskal-Wallis o chi-squa e es s o con inuous and ca ego ical a iables. Mo eo e , we pe o med a wo-by- wo compa ison be ween he g oups: posi i e PCR, nega i e PCR wi h posi i e IgG ega dless o IgM, and nega i e PCR wi h nega i e esul s o IgG and IgM an ibodies using Mann-Whi ney o chi-squa ed es s. Analyses we e pe o med using R e sion 3.6.2 language p o- g amming (R Founda ion o S a is ical Compu ing, Vienna, Aus ia), and p- alues <0.05 we e conside ed signi ican . 3. Resul s Du ing he s udy pe iod s udy, 1211 p egnan women we e admi ed o labo and deli e y and subjec ed o SARS-CoV-2 sc eening using PCR and se ological examina ion o an i-SARS-CoV-2 an ibodies (IgG and IgM; Fig. 1). None o he g a ids we e a ec ed by SARS-CoV-2 pneu- monia o any o he se e e clinical symp om du ing he s udy pe iod. The p e alence o SARS-CoV-2 in ec ion was 5.4%, co esponding o 43 p e ious SARS-CoV-2 exposu es and 22 ongoing in ec ions, wo o hem had co ona i us disease 2019 (COVID-19) symp oms a he ime o admission, and 10 we e asymp oma ic cases wi hou an ibodies. Bo h PCR and an ibodies o SARS-CoV-2 we e nega i e in 1146 women. None o he sc eened mo he s we e admi ed o COVID-19 be o e o R. Sa i ´ on-Co nudella e al. Li e Sciences 271 (2021) 119200 3 a e deli e y, no we e any o he newbo ns equi ed o s ay in he neona al ICU. All newbo ns o 22 mo he s wi h posi i e PCR on admission we e PCR nega i e. Du ing he s udy pe iod, he e we e no p egnan women admi ed o he Depa men o In ec ious Diseases o he In ensi e Ca e Uni s (ICUs). Table 1 shows he baseline cha ac e is ics o he h ee g oups s ud- ied: (i) p egnan women wi h ongoing SARS-CoV-2 in ec ion, (ii) p e- ious i al in ec ion, and (iii) no e idence o in ec ion. We ound s a is ically signi ican di e ences in ma e nal age (p =0.028), pa i y (p =0.023), and p eges a ional diabe es melli us (p =0.022) a es. O he clinical a iables s udied (ch onic hype ension, ges a ional diabe es melli us, and obs e ic ou comes) did no show signi ican di e ences. Table 2 displays he ma e nal and pe ina al ad e se ou comes, wi h no signi ican di e ences among he h ee p ede ined g oups o ma e nal in apa um e e , pos pa um u e ine hemo hage o a ony, hype en- si e diso de s o p egnancy, e al g ow h es ic ion, 5-min Apga sco e <7, a e ial co d blood pH <7.10, ins umen al deli e y o NRFS, cesa ean deli e y o NRFS, s illbi h and neona al ICU admission. The Hospi al p o ocols did no include epe i ion o se ological es ing. The e we e simila esul s in he wo-by- wo compa isons among he h ee s udied g oups (Table 3), wi h s a is ically signi ican di e ences in mode o deli e y (p =0.03) in he compa ison o (i) SARS-CoV-2 PCR nega i e/IgG posi i e e sus; (ii) SARS-CoV-2 PCR nega i e/IgG nega- i e; and ma e nal age (p =0.015), pa i y (p =0.02), and p eges a ional diabe es melli us (p =0.008) in he compa ison o (iii) SARS-CoV-2 PCR posi i e e sus (i ) SARS-CoV-2 PCR nega i e/IgG nega i e. As shown in Table 3, he e we e no signi ican di e ences among he s udied g oups o o he a iables: ma e nal age, pa i y, ch onic hype ension, hype ensi e diso de s o p egnancy, p eges a ional diabe es melli us, ges a ional diabe es melli us, e e , hemo hage o pos pa um u e ine a ony, newbo n sex, mode o deli e y, ges a ional age a bi h, bi h and pe cen ile bi h weigh , a e ial co d blood pH, e al g ow h es ic ion, 5-min Apga sco e <7, a e ial co d blood pH <7.10, ins umen al and cesa ean deli e y o NRFS, s illbi h and neona al ICU admission. 4. Discussion O he 1211 p egnan women sc eened o SARS-CoV-2 exposu e, 43 had a p e ious i al exposu e wi h posi i e IgG es , and 1146 women we e nega i e o bo h PCR and immunoglobulin G and M es s. The p e alence o SARS-CoV-2 in ec ion in p egnan women was 5.4%. Du ing he s udy pe iod, none o he women o he newbo ns had pneumonia o any o he symp oms ha equi ed hei admission o he in ensi e ca e uni . The e we e no di e ences in ma e nal o neona al ou comes ac oss he h ee g oups o p egnan women (ongoing in ec- ion, p e ious in ec ion, and women wi h no e idence o SARS-CoV-2 in ec ion). A la ge numbe o publica ions du ing he i s wa e o he SARS- CoV-2 epidemic we e based on se e e o ms o he in ec ion. Howe - e , he i al in ec ion can display only mild symp oms o e en be asymp oma ic. Se e al epo s ha e desc ibed sc eening wi h PCR in p egnan women admi ed o labo and deli e y since he beginning o he pandemic si ua ion, wi h esul s anging om less han 1% [13,17] o 15–20% [11,12]. This a iabili y may be due o se e al ac o s, including di e ences among he s udied popula ions, li es yle, heal h- ca e sys ems, and ec ui men o s udied women in di e en phases o Fig. 1. Flowcha o uni e sal sc eening wi h polyme ase chain eac ion (PCR) and immunoglobulins G and M in spon aneous o planned deli e ies (labo induc ion o cesa ean deli e y). R. Sa i ´ on-Co nudella e al. Li e Sciences 271 (2021) 119200 4 he SARS-CoV-2 pandemic. In p egnan women du ing hei i s imes e , C o e o e al. [20], in Ba celona (Spain), epo ed a highe p e alence o SARS-CoV-2 by se ological es ing (14%) han by PCR (0.78%) in 871 women, a ending a i s - imes e sc eening (n =372) o deli e y (n =502). Ou p elimina y s udy o 266 p egnan women s udied du ing deli e y in Za agoza (Spain) ound a p e alence o 6.8% o se ological es s and 2.2% o he PCR p ocedu e [23], whe eas p e alence o he p esen sample o 1211 women om Mad id and Za agoza we e 3.6% and 1.8%, espec i ely. Ou se op e alence o SARS-CoV-2 du ing labo and deli e y is close o he 5.0% epo ed a e in he main Spanish popula ion [24]. The ma e nal and neona al clinical cou se o ou s udied popula ion showed simila ma e nal and pe ina al ou comes when compa ing women wi h and wi hou SARS-CoV-2 in ec ion. P e ious s udies using only PCR es ing du ing labo and deli e y, in bo h symp oma ic and asymp oma ic COVID-19 pa ien s, epo ed high a es o cesa ean de- li e y among hese women [15,16]. In a se ies o 675 p egnan women om New Yo k admi ed o labo and deli e y, P abhu e al. [15] e- po ed a sligh inc ease in he a e o cesa ean deli e y in symp oma ic COVID-19 women (46.7%) compa ed o asymp oma ic ones (45.5%). Díaz-Co ill´ on e al. [16] in Chile desc ibed ano he s udy o SARS- CoV-2 in 583 pa ien s using only PCR du ing labo and deli e y admission. They epo ed a 43.2% a e o asymp oma ic women and no signi ican di e ences in pe ina al ou comes, bu a end owa ds a highe a e o p e e m bi h. In ou coho , we had a low a e o cesa ean deli e ies, and he e we e no di e ences in aginal o cesa ean deli e y a es among any o he g oups. Howe e , ou a e o symp oma ic SARS- CoV-2 in ec ions was lowe han hose epo ed in bo h he New Yo k and Chilean s udies. The e o e, we mus exe cise cau ion when in e - p e ing he cesa ean sec ion a es and o he ou comes o p egnan women included in uni e sal PCR sc eening, compa ed o hose o symp oma ic cases. Ege up e al. [25] s udied a popula ion o 1313 p egnan women, in Copenhagen (Denma k), om Ap il o July 2020, including 28 cases o posi i e an ibodies and one case o posi i e PCR. The s udy concluded ha SARS-CoV-2 in ec ion was no associa ed wi h obs e ic complica- ions in p egnan women who had had he disease. In ou s udy wi h 43 IgG posi i e women, we also ound no di e ences in ad e se pe ina al e ec s be ween he 22 cases wi h posi i e PCR, as compa ed wi h women no exposed o he SARS-CoV-2 in ec ion. Some au ho s ha e desc ibed highe p e e m bi h a es associa ed wi h COVID-19 in p egnan women [26,27]. We did no ind a highe a e o p e e m bi h in ongoing o p e ious SARS-CoV-2 in ec ions p obably due o he mild clinical cou se in ou pa ien s, whe eas indings may di e in symp- oma ic coho s. Ou esul s i well wi h he Flanne y e al. s udy [28] pe o med in wo cen e s o Philadelphia (Pennsyl ania, US), using bo h he PCR and se ological es s. They epo ed 80 posi i e se ological es s in a popula ion o 1293 women o di e en e hnici ies du ing labo and deli e y, including 6.2% posi i e IgG and/o IgM SARS-CoV-2 women. This Ame ican s udy, and ou esul s, poin ou he con enience o s udying IgG and IgM o ob ain mo e p ecise in o ma ion han only using PCR in pa u ien s a isk o in ec ion by SARS-CoV-2. The Elsha eey e al. [29] e iew epo ed 95.6% o mild cases in p egnan women wi h SARS-CoV-2 in ec ion, bu a 4.41% a e o admission o ma e nal ICU wi h 1.67% equi ing mechanical Table 1 Ma e nal cha ac e is ics and obs e ic ou comes in h ee g oups o p egnan women s udied du ing labo and deli e y: (i) p egnan women wi h ongoing SARS-CoV-2 in ec ion, (ii) p e ious i al in ec ion, and (iii) no e idence o i al in ec ion. Resul s exp essed as n (pe cen ages) and median (in e qua ile ange). Posi i e PCR Nega i e PCR Posi i e IgG Nega i e PCR Nega i e IgG p- alue Miguel Se e Hospi al 13 (73.4) 24 (59.1) 841 (55.8) 0.015 Villalba Gene al Hospi al 9 (26.6) 19 (40.9) 305 (44.2) To al p egnan women 22 (1.8) 43 (3.6) 1146 (94.6) Ma e nal cha ac e is ics Median ma e nal age 29.2 (24.4–35.4) 33.0 (27.8–36.7) 33.5 (29.6–37.3) 0.028 Pa i y 0 13 (59.1) 19 (44.2) 587 (51.2) 0.023 1 3 (13.6) 13 (30.2) 381 (33.2) 2 2 (9.1) 9 (20.9) 120 (10.5) ≥3 4 (18.2) 2 (4.7) 58 (5.1) Ch onic hype ension 0 (0) 0 (0) 15 (1.3) 0.483 P eges a ional diabe es melli us 1 (4.5) 0 (0) 5 (0.4) 0.022 Ges a ional diabe es melli us 2 (9.1) 7 (16.3) 172 (15.0) 0.720 Obs e ics ou comes Newbo n sex Male 13 (59.1) 17 (39.5) 539 (47.0) 0.324 Female 9 (40.9) 26 (60.5) 607 (53.0) Mode o deli e y Vaginal deli e y 16 (72.7) 38 (88.4) 798 (69.6) 0.129 Ins umen al deli e y 3 (13.6) 3 (7.0) 192 (16.8) Cesa ean deli e y 3 (13.6) 2 (4.7) 156 (13.6) Ges a ional age (weeks) 39.6 (38.6–40.7) 39.7 (38.7–40.6) 39.9 (39.0–40.3) 0.976 Bi h weigh (g ams) 3387 (3032–3700) 3335 (2959–3577) 3260 (2970–3552) 0.484 Bi h weigh (pe cen ile) 55.0 (29.1–86.6) 54.8 (34.9–75.9) 50.9 (25.9–76.3) 0.493 A e ial co d blood pH 7.28 (7.23–7.33) 7.27 (7.24–7.32) 7.27 (7.22–7.33) 0.977 Ig: immunoglobulin; PCR: polyme ase chain eac ion. Table 2 Ad e se ma e nal and pe ina al ou comes (pe cen ages) in h ee g oups o p egnan women s udied du ing labo and deli e y: (i) g a ids wi h ongoing co ona i us 2019 in ec ion, (ii) p e ious i al in ec ion, and (iii) no e idence o i al in ec ion. Ou comes SARS- CoV-2 posi i e PCR SARS-CoV-2 nega i e PCR and posi i e IgG SARS-CoV-2 bo h nega i e PCR and IgG P Ad e se ma e nal ou comes Ma e nal in apa um e e 0 (0) 3 (7.1) 141 (12.3) 0.151 Hemo hage o pos pa um u e ine a ony 1 (5) 0 (0) 27 (2.4) 0.475 Hype ensi e diso de s o p egnancy 0 (0) 0 (0) 26 (2.3) 0.481 Ad e se pe ina al ou comes Fe al g ow h es ic ion (pe cen ile<3) 0 (0) 0 (0) 45 (3.9) 0.271 5-min Apga sco e < 7 0 (0) 0 (0) 7 (0.6) 0.818 A e ial co d blood pH <7.10 0 (0) 1 (2.3) 32 (2.8) 0.718 Ins umen al deli e y o NRFS 0 (0) 0 (0) 16 (1.4) 0.631 Cesa ean deli e y o NRFS 0 (0) 0 (0) 23 (2) 0.514 S illbi h 0 (0) 0 (0) 2 (0.2) 0.944 Neona al in ensi e ca e uni admission 0 (0) 2 (4.7) 35 (3.1) 0.891 Ig: immunoglobulin; NRFS: non eassu ing e al s a us; PCR: polyme ase chain eac ion, R. Sa i ´ on-Co nudella e al. Li e Sciences 271 (2021) 119200 5 en ila ion. Acco ding o his e iew, he si ua ion may no be as a o able as i ini ially seemed o p egnan women wi h COVID-19, al hough included epo s ocused on s udying women wi h symp om- a ic COVID-19. In s udies on uni e sal sc eening o women admi ed o labo and deli e y, he igu es a e much mo e eassu ing. Thus, P abhu e al. [15], in New Yo k, desc ibed a mild cou se o COVID-19 disease among hei coho o 675 p egnan women, wi h only one case o admission o he ma e nal ICU. In Chile, Díaz-Co ill´ on e al. [16] e- po ed a 0.51% admission a e o he ma e nal ICU and mechanical en ila ion. In ou s udy, we did no ha e se e e COVID-19 cases. All o ou cases had mild symp oms, and none equi ed admission o he ICU, acco ding o he Wu e al. disease se e i y cha ac e is ics [30]. I seems ha SARS-CoV-2 in ec ion du ing p egnancy is less se e e han o he co ona i us espi a o y in ec ions due o he educed p o-in lamma o y esponse ha is associa ed wi h a lowe le el cy okine s o m du ing p egnancy [31], and he low SARS-CoV-2 i e s in co d blood plasma [32]. Howe e , he ecen Na ional Mexican P ospec i e Coho o P egnan Women con i ms ha he SARS-CoV-2 in ec ion is associa ed wi h a highe isk o dea h, in uba ion, and ICU admissions in p egnan women [10]. These he e ogeneous esul s may be ela ed o he a i- abili y in SARS-CoV-2 p e alence in di e en wo ld egions, and also in heal hca e access and quali y, li es yle, and o he ac o s [33–35]. Rega ding he ela ionship be ween SARS-CoV-2 and pe ina al mo bidi y, cases desc ibed in symp oma ic coho s o p ema u e de- li e ies ha e been mainly associa ed wi h ia ogenesis, ending he p egnancy ea ly o main ain ma e nal well-being [5,36,37]. P abhu e al. [15] and Díaz-Co ill´ on e al. [16] showed no inc ease in ad e se pe ina al ou comes in ma e nal PCR posi i e cases in uni e sal sc eening a labo and deli e y. Lingkong Zeng e al. [38] desc ibed a case o pneumonia in a SARS-CoV-2 in ec ed neona e, al hough hey poin ed ou ha he symp oms could ha e been due o p ema u i y, asphyxia, o sepsis, a he han o SARS-CoV-2 in ec ion. In ou s udy popula ion, he ma e nal and pe ina al ou comes we e no signi ican ly di e en be- ween p egnan women wi h and hose wi hou SARS-CoV-2 in ec ion al hough, as p e iously men ioned, none o hese women had pneu- monia o o he clinical symp oms. The isk o e ical ansmission o SARS-CoV2 du ing labo and deli e y is s ill no clea [6]. Some esul s sus ain ha he e is li le e idence o he SARS-CoV-2 e ical ansmission [39]. Howe e , he e a e also some epo s o asymp oma ic posi i e SARS-COV-2 PCRs in he newbo ns o in ec ed mo he s [16,38,40]. Yee e al. [8] epo ed i e neona es wi h posi i e swab es s ha could ha e become in ec ed du ing aginal o cesa ean deli e y. A ecen me a-analysis calcula ed a 5.3% a e o e ical ansmission and a posi i e SARS-CoV-2 es a e o 8% in neona es om mo he s wi h COVID-19 [41]. Howe e , Alga oba e al. [42] ecen ly epo ed he p esence o SARS-CoV-2 in he placen a, using elec on mic oscopy, in a g a id wi h pneumonia ea ed wi h co icos e oids o e al lung ma u i y be o e a p e e m cesa ean deli e y. Pe ina al esul s a e eassu ing, and no neona al complica ions we e associa ed wi h ma e nal SARS-COV-2 in ec ion in p e ious s udies [15,16]. Ege up e al. [25] also ound no di e ences be ween pa ien s wi h posi i e e sus nega i e an ibodies in neona al complica ions. We ound no signi ican di e ences in APOs among ou h ee g oups, and none o he neona al in ec ions we e by SARS-CoV-2. Ou s udy is a la ge coho s udied o e se e al mon hs a wo ins i u ions o he Spanish Na ional Heal h Sys em ha p o ide heal hca e o he en i e popula ion. We acknowledge ha ou s udy has some limi a ions. Fi s ly, some women may ha e omi ed epo ing symp oms because o hei ea o he implica ions o ha ing a co ona i us in ec ion. Ano he limi a ion is he small numbe o in ec ed women o epo ep esen a i e esul s o bo h ma e nal and pe ina al ad e se ou comes, al hough ou esul s a e in line wi h simila da a. Rega ding he p egnan women wi h a p e ious in ec ion, we we e unable o de e mine when he in ec ion migh ha e occu ed, and we did no know i his in luenced he ou comes o he p egnancy. Mo eo e , he de ec ion ki s used in bo h hospi als we e om di e en b ands, so could ha e had di e en sensi i i ies and speci ici ies. Finally, ou s udy is an obse a ional clinical esea ch, and we acknowledge ha bo h alse posi i e and nega i e esul s may be possible. 5. Conclusion P egnan women wi h asymp oma ic SARS-CoV-2 in ec ion o wi h mild clinical symp oms de ec ed a labo and deli e y do no ha e highe a es o ad e se ma e nal o pe ina al ou comes han women wi h nega i e PCR and immunoglobulin es s. The key o ma e nal o pe ina al ad e se e ec s is he clinical se e i y o SARS-CoV-2 in ec ion in he p egnan woman. We p o ide e idence ha he s udied neona es we e no in ec ed in he u e us o du ing deli e y. Table 3 S a is ical signi icance (p alue) o di e en compa isons o p egnan women SARS-CoV-2 acco ding o polyme ase chain eac ion (PCR) posi i e/nega i e and immunoglobulin (Ig) G posi i e/nega i e in h ee g oups o p egnan women du ing labo and deli e y epo ed by p- alues o Wilcoxon es compa isons. SARS-CoV-2 PCR posi i e e sus bo h nega i e PCR and IgG SARS-CoV-2 PCR nega i e and IgG posi i e e sus PCR nega i e and IgG nega i e SARS-CoV-2 PCR posi i e e sus PCR nega i e and IgG posi i e Ma e nal ou comes Ma e nal age (yea s) 0.015 0.245 0.254 Pa i y 0.020 0.194 0.094 Como bidi ies Ch onic hype ension 0.589 0.450 0.999 Hype ensi e diso de s o p egnancy 0.475 0.318 0.999 P eges a ional diabe es melli us 0.008 0.664 0.156 Ges a ional diabe es melli us 0.440 0.819 0.427 Fe e 0.079 0.293 0.204 Hemo hage o pos pa um u e ine a ony 0.506 0.308 0.158 Obs e ic ou comes Newbo n sex 0.364 0.417 0.217 Mode o deli e y 0.925 0.030 0.265 Ges a ional age a bi h (weeks) 0.892 0.877 0.708 Bi h weigh (g ams) 0.329 0.465 0.713 Pe cen ile bi h weigh 0.356 0.439 0.731 A e ial co d blood pH 0.828 0.992 0.906 Pa hological indings p- alue p- alue p- alue Fe al g ow h es ic ion (pe cen ile <3) 0.343 0.185 0.999 5-min Apga sco e < 7 0.713 0.611 0.999 A e ial co d blood pH <7.10 0.426 0.872 0.487 Ins umen al deli e y o NRFS 0.402 0.247 0.999 Cesa ean deli e y o NRFS 0.502 0.353 0.999 S illbi h 0.844 0.786 0.999 Neona al ICU admission 0.404 0.533 0.298 NRFS: non eassu ing e al s a us. R. Sa i ´ on-Co nudella e al. Li e Sciences 271 (2021) 119200 6 CRediT au ho ship con ibu ion s a emen RSC, AV, LME and FRPL con ibu ed o he concep ion o he s udy. RSC, LME, FRPL and BCL con ibu ed o he design o he clinical wo k. RSC, AV, MT, BRS, MAG, JZ and SR ca ied ou da a acquisi ion. LME and FRPL pe o med s a is ical analyses. All au ho s we e in ol ed in he in e p e a ion o he s udy esul s, as well as he d a ing and e i- sion o he manusc ip . All app o ed he inal e sion o be published. Decla a ion o compe ing in e es This esea ch did no ecei e a speci ic g an om unding agencies in he public, comme cial, o no - o -p o i sec o s. The au ho s decla e ha he e a e no con lic s o in e es . Acknowledgemen We g a e ully hank all he s a a Villalba Gene al Uni e si y Hospi al, Mad id, and a Miguel Se e Uni e si y Hospi al, Za agoza, Spain who ha e ough agains he SARS-CoV-2 epidemic. Funding This esea ch did no ecei e any g an om unding agencies. 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