Perinatal Outcomes at Birth in Women Infected and Non-Infected with SARS-CoV-2: A Retrospective Study

Citation: Vila-Candel, R.; Martin-Arribas, A.; Castro-Sánchez, E.; Escuriet, R.; Martin-Moreno, J.M. Perinatal Outcomes at Birth in Women Infected and Non-Infected with SARS-CoV-2: A Retrospective Study. Healthcare 2023,11, 2833. https://doi.org/10.3390/ healthcare11212833 Academic Editors: Abdel-Latif Mohamed and Giuseppe Rizzo Received: 1 September 2023 Revised: 24 October 2023 Accepted: 25 October 2023 Published: 27 October 2023 Copyright: © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). healthcare Article Perinatal Outcomes at Birth in Women Infected and Non-Infected with SARS-CoV-2: A Retrospective Study Rafael Vila-Candel 1,2,3 , Anna Martin-Arribas 4,* , Enrique Castro-Sánchez 5,6,7 , Ramón Escuriet 4,8 and Jose M. Martin-Moreno 9,10 1Sciences Faculty, Universidad Internacional de Valencia—VIU, 46002 Valencia, Spain; [email protected] 2Department of Obstetrics and Gynecology, Hospital Universitario de la Ribera, 46600 Alzira, Spain 3Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), 46020 Valencia, Spain 4Ghenders Research Group, School of Health Sciences Blanquerna, Universitat Ramon Lull, 08025 Barcelona, Spain; r[email protected] 5College of Business, Arts, and Social Sciences, Brunel University London, Uxbridge UB8 3PH, UK; [email protected] 6Health Protection Research Unit, Healthcare-Associated Infections and Antimicrobial Resistance, Imperial College London, London SW7 2BX, UK 7Research Group on Global Health and Human Development, University of the Balearic Islands, 07122 Palma de Mallorca, Spain 8Catalan Health Service, Government of Barcelona, 08014 Barcelona, Spain 9Department of Preventive Medicine and Public Health, Universitat de València, 46010 Valencia, Spain 10 Biomedical Research Institute INCLIVA, Clinic University Hospital, 46010 Valencia, Spain *Correspondence: [email protected] Abstract: Background: Coronavirus disease 2019 (COVID-19) was declared as a pandemic and public health emergency on 11 March 2020 by the World Health Organization. Different clinical trials on the efficacy of mRNA vaccination have excluded pregnant women, leading to a lack of empirical evidence on the efficacy of the vaccine in this population. The aim of the study was to examine the association between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection at birth and adverse perinatal outcomes in infected and non-infected women from a university hospital in Spain. Methods: The data were obtained from electronic health records from 1 March 2020 to 28 February 2022. A bivariate descriptive analysis was performed, comparing women with and without confirmed SARS-CoV-2 infection during pregnancy using the chi-square test. A multivariate logistic regression was complementarily conducted to determine whether SARS-CoV-2 infection increases the risk of adverse obstetric and perinatal outcomes. Results: A total of 2676 women were divided into two groups: non-infected with SARS-CoV-2 (n= 2624) and infected with SARS-CoV-2 (n= 52). Infected women were primarily multiparous (p< 0.03) and had received an incomplete vaccination regimen (p< 0.001). A greater incidence of premature rupture of membranes (p< 0.04) was observed among the non-infected women. Pertaining to perinatal outcomes, there was a notable rise in NICU admissions (p< 0.014), coupled with an extended duration of stay (p< 0.04), for neonates born to infected mothers in comparison to their non-infected counterparts. Conclusion: Although SARS-CoV-2 infection may pose significant risks to pregnant women and their infants, adverse obstetrical/puerperal outcomes do not significantly differ between women infected and non-infected to SARS-CoV-2 in our study. NICU admissions were higher for neonates born to infected mothers. Additionally, coronavirus disease 2019 vaccination during pregnancy is not associated with severe adverse perinatal outcomes. Keywords: SARS-CoV-2; vaccination; women’s health; perinatal outcomes; adverse outcomes Healthcare 2023,11, 2833. https://doi.org/10.3390/healthcare11212833 https://www.mdpi.com/journal/healthcare Healthcare 2023,11, 2833 2 of 18 1. Introduction Coronavirus disease 2019 (COVID-19) was declared as a pandemic and public health emergency on 11 March 2020 by the World Health Organization. Since the first detected case of COVID-19 in Wuhan, Hubei, China, in December 2019, the infection spread to the rest of the world with an alarming number of cases [1,2]. The initial transmission pattern has been suggested to be zoonotic, while the current spread has been from person to person through airborne transmission following close contact with an infected person or direct contact with contaminated surfaces [ 3 , 4 ]. The risk of vertical transmission appears to be low (approximately 0–4%) and, therefore, of modest relevance [ 5 – 7 ]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be detected in amniotic fluid, but this is exceptional. Although SARS-CoV-2 has been isolated in the placenta, vertical transmission of the virus appears to be rare and limited to cases of severe maternal infection [ 8 ]. Most described cases of infection in newborns are from horizontal transmission. In addition, the virus has not been detected in vaginal secretions or breast milk [ 8 – 10 ]. The available data suggest a range of viral RNA presence in milk samples, spanning from 2% to 6%. A recent systematic review [ 11 ] of lactating individuals affected by COVID-19 revealed a 13.2% detection rate of SARS-CoV-2 RNA. Similarly, another systematic review [ 12 ] indicated around a 2% detection rate of RNA in breast milk. Among these studies, the most extensive involved 110 women from the US [ 13 ], 65 of whom tested positive for SARS-CoV-2. In this study, 6% of the milk samples exhibited SARS-CoV-2 RNA presence; however, no infectious particles were cultured from these samples. Notably, a recent clinical trial yielded different results, as no SARS-CoV-2 RNA was detected in any of the breast milk samples [ 14 ]. The findings of this trial endorse official recommendations that underline the safety of breastfeeding during COVID-19. This perspective prioritizes breastfeeding due to its potential to confer maternal–neonatal benefits. COVID-19 may be asymptomatic in up to 75% of pregnant women [ 15 ]. When symptoms appear, the infection is classified according to the severity of respiratory symptoms as mild, moderate, and severe [ 4 ]. The majority of symptomatic cases during gestation present a mild infection (85%) [ 16 ]. The most frequent symptoms during pregnancy are fever (40%) and cough (39%), while other less frequent symptoms are myalgia, dyspnea, odynophagia, anosmia, expectoration, headache, and diarrhea [5]. Pregnant women are at a higher risk of severe infection-related complications with respect to the non-pregnant population, especially in the third trimester and when the following risk factors are present: advanced maternal age, high body mass index (BMI of >30 kg/m 2 ), chronic hypertension, and/or pregestational diabetes [ 17 ]. Approximately 15% of COVID-19 cases progress to severe forms [ 18 ]. Approximately 5% of infected pregnant women may require admission to an intensive care unit (ICU), and 3% may require invasive ventilation [ 7 ]. The rate of mortality in pregnant women ranges from 0.1% to 1.2%. Severe forms present the following main complications: severe pneumonia, acute respiratory distress syndrome, thromboembolic disease, bacterial respiratory superinfection, cardiac alterations, encephalitis, sepsis, and septic shock [6,7,19]. Regarding fetal or neonatal complications, the current data do not suggest an increased risk of miscarriage or early gestational loss in pregnant women with COVID-19 [ 7 ]. Similarly, severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus have not been reported to demonstrate a clear causal relationship with these complications [ 20 ]. No increased risk of congenital defects has also been described [ 9 ]. The main perinatal complication associated with COVID-19 is prematurity, with rates around 20%, mainly at the expense of iatrogenic prematurity [ 5 , 7 ]. There may be placental involvement and anatomopathological alterations in the form of vascular malperfusion or intervillous fibrin deposits whose consequences at the fetal level have yet to be determined [ 5 ]. No significant differences in other perinatal outcomes have been found among neonates born to mothers with COVID-19, although 25% are admitted to a neonatal care Healthcare 2023,11, 2833 3 of 18 unit [ 8 ]. Regarding neonatal COVID-19, 50% of cases generally present to adult clinics with comparable results in terms of symptomatology and analytical and imaging findings [7]. Between 2020 and 2022, Spain experienced six pandemic waves of COVID-19, each presenting distinct challenges. Throughout this period, stringent measures were enforced during states of emergency to curb viral transmission [ 21 ]. These measures had direct repercussions on the medical care provided to pregnant women, resulting in discernible adjustments to obstetric protocols [ 22 , 23 ]. Scientific societies remained dynamic, continually adapting obstetric care protocols in response to evolving epidemiological trends [ 5 ]. The intricate interplay between COVID-19 prevention and ensuring safe care for mothers and newborns assumed paramount importance. However, across these successive pandemic waves, certain indispensable practices in maternal and childbirth care underwent necessary adaptation or suspension to mitigate virus spread. As the landscape evolved, practices like labor companionship, early skinto-skin contact, and rooming-in were supplanted by measures such as mother–infant separation and neonatal intensive care unit (NICU) admission [ 23 ]. While these adjustments aimed to safeguard both mothers and medical personnel, concerns about care quality inevitably arose. The modification of these practices bore negative implications for the maternal experience and neonatal health, hampering mother–infant interaction and impeding breastfeeding promotion [24]. As the pandemic progressed, healthcare professionals persevered in their efforts to strike a delicate balance between preventive measures and maintaining a warm, secure environment during the birthing process. This underscored the urgency of embracing adaptable, evidence-based approaches to safeguard maternal and neonatal health amid health crises and epidemiological fluctuations [22]. In 2021, the vaccination campaign first expanded to encompass adults, and subsequently, commencing December of that year, extended to include pregnant women [ 25 ]. Robust studies unequivocally endorsed the safety and efficacy of vaccines, driving a gradual acceptance and favorable response within the populace [ 6 , 9 , 26 ]. This multifaceted interplay between pandemic waves, evolving protocols, and vaccination efforts underscores the need for dynamic, evidence-driven strategies to ensure optimal care provision during times of crisis. Although a published series of vaccinations during pregnancy still include few cases, the currently available COVID-19 vaccines are not expected to pose a problem during pregnancy and lactation [ 6 , 9 , 26 , 27 ]. The recent recommendation is to offer a messenger RNA (mRNA) vaccine to all pregnant women following established vaccination schedules and especially to pregnant women with comorbidities (e.g., patients who underwent transplantation, who are immunosuppressed, or who have cardiopulmonary, renal, oncologic, or other conditions) [ 28 ]. The ideal time for administration is the second trimester. However, if the epidemiological risk is high or there are comorbidities, there is no inconvenience in administering the vaccine in the first trimester [29]. Different clinical trials on the efficacy of mRNA vaccination have excluded pregnant women, leading to a lack of empirical evidence on the efficacy of the vaccine in this population [ 26 , 30 ]. Therefore, vaccine safety and efficacy during pregnancy are mainly evaluated through observational epidemiological studies [31]. In this study, at the beginning of the pandemic, where vaccination efforts were nascent and the circulating virus reached considerably higher levels within the community, our aim was to explore the association between SARS-CoV-2 infection at birth and adverse obstetrical–neonatal outcomes from a university hospital in Spain. In addition, we assessed the proportion of neonates with reverse transcription polymerase chain reaction (RT-PCR)-detectable SARS-CoV-2 from all births among women with COVID-19 diagnosed at the onset of labor. Healthcare 2023,11, 2833 4 of 18 2. Materials and Methods This observational, retrospective study (clinical/epidemiological, descriptive, and analytical in nature) was conducted among pregnant women who visited the Hospital Universitario de la Ribera (HULR) for delivery from 1 March 2020 to 28 February 2022. The HULR is a regional hospital with a population area of 250,000 inhabitants and assists an average of 1300 deliveries per year. Deliveries of less than 34 weeks of gestation are referred to a referral hospital. The women were allocated into infected and non-infected groups based on the results of RT-PCR or antigen testing (nasopharyngeal exudate) for SARS-CoV-2 at hospital admission. The infected group included women positive for SARS-CoV-2 on RT-PCR or antigen testing during delivery, and non-infected group included women with a negative result. Information on COVID-19 vaccination was collected from both unvaccinated and vaccinated women. Women who received at least one dose of the COVID-19 vaccine either before or during the current pregnancy were included in the vaccinated cohort. Although this group was labeled as “vaccinated”, some women did not follow the full vaccination schedule at the time of delivery. Pregnant women infected with SARS-CoV-2 admitted for medical/surgical reasons other than childbirth were excluded. 2.1. Sample Size From 1 March 2020 to 28 February 2022, the entire population whose deliveries were attended during the study period was considered. In the first year (1 March 2020, to 28 February 2021 ), there were 1236 deliveries. Similarly, in the second year (1 March 2021, to 28 February 2022), there were 1440 deliveries. 2.2. Data Collection The information necessary for inclusion in the study was obtained from two different sources: (1) electronic medical records of specialized care, from which variables related to care during childbirth and puerperium and subsequent complications were collected, and (2) primary care medical records, from which the vaccination status. The obstetrical outcomes evaluated were as follows: premature rupture of membranes (PROM), preterm birth (<37 weeks of gestation), placental abruption, antepartum hemorrhage, postpartum hemorrhage, cesarean section, instrumental delivery, fetal distress (defined by a healthcare provider), fetal growth restriction (estimated fetal weight below the third percentile), pregnancy-induced hypertension, and gestational diabetes. The COVID-19-related outcomes were presenting signs/symptoms, admission to an intensive care unit (ICU), length of ICU stay of more than 4 days, intubation, supplemental oxygen, cardiac manifestations (myocardial infarction, cardiomyopathy, or arrhythmia), neurologic manifestations (seizures, hemorrhagic or ischemic stroke, or coma), thrombotic manifestations (deep vein thrombosis, pulmonary embolism, or arterial thrombosis), coagulopathy, and maternal death during admission. The neonatal outcomes were small for gestational age (SGE: birthweight below the 10th percentile), large for gestational age (LGE: birthweight above the 90th percentile), Apgar score of <7 at 5 min, neonatal intensive care unit (NICU) admission, length of neonatal ICU stay of more than 4 days, respiratory distress, ventilator support, SARS-CoV-2 infection, hypoxic ischemic encephalopathy, and neonatal death. Other covariates included sociodemographic and medical characteristics that could act as potential risk factors: maternal age, parity, gestational age at birth, date of birth, country of origin, gestational pathologies (thyroid, gestational diabetes and preeclampsia), other clinical variables (maternal obesity, asthma, or smoker), mRNA SARS-CoV-2 vaccine (Pfizer-BioNTech), number of doses, and time between last vaccine administration and infection (when infected) (Figure 1). Healthcare 2023,11, 2833 5 of 18 Healthcare2023,11,xFORPEERREVIEW5of18    Figure1. Datacollectionflowchart. 2.3.StatisticalAnalysis Wefirstperformedaunivariatedescriptiveanalysisofthebirthcharacteristics.Quantitativevariablesweresummarizedasmeansandstandarddeviationsandcategoricalvariablesasabsoluteandrelativefrequencies. Subsequently,abivariatedescriptiveanalysiswasconducted,comparingtheinfected andnon-infectedgroups.CategoricalvariableswerecomparedusingtheChi-squaretest andquantitativevariablesusingANOVA.Thecomputationofoddsratiosandtheircorrespondingconfidenceintervals,accompaniedbyp-valuesderivedfromlog-odds throughtheutilizationoftheWaldtest,wasexecutedbyemployingaseriesoflogistic regressionmodelsfeaturingasoleindependentvariable[32].Intheinvestigationpertainingtodistinctvaccinationstatuses(unvaccinated,incompleteregimen,completeregimen),ananalogousmethodologywasapplied.However,inthisinstance,amultinomial regressionframeworkwithalogitlinkfunctionwasemployed.Finally,amultivariate Figure 1. Data collection flowchart. 2.3. Statistical Analysis We first performed a univariate descriptive analysis of the birth characteristics. Quantitative variables were summarized as means and standard deviations and categorical variables as absolute and relative frequencies. Subsequently, a bivariate descriptive analysis was conducted, comparing the infected and non-infected groups. Categorical variables were compared using the Chi-square test and quantitative variables using ANOVA. The computation of odds ratios and their corresponding confidence intervals, accompanied by p-values derived from log-odds through the utilization of the Wald test, was executed by employing a series of logistic regression models featuring a sole independent variable [ 32 ]. In the investigation pertaining to distinct vaccination statuses (unvaccinated, incomplete regimen, complete regimen), an Healthcare 2023,11, 2833 6 of 18 analogous methodology was applied. However, in this instance, a multinomial regression framework with a logit link function was employed. Finally, a multivariate logistic regression analysis using the backward Wald method was performed to determine whether SARS-CoV-2 infection increases the risk of adverse obstetric and perinatal outcomes. The significance of SARS-CoV-2 infection for each outcome variable and ORs were evaluated. Statistical significance was set at a p-value of ≤ 0.05. Data were statistically analyzed using R (version 4.0.2). 2.4. Ethics Statement Neither informed consent nor a patient information sheet was required owing to the retrospective nature of the study. Only electronic medical records were reviewed, and no contact was made at any time with the patients whose data were analyzed. No identifying data of the women and/or their newborns were included in the data collection notebook. The study complied with the Helsinki Recommendations for biomedical studies and was approved by the Research and Ethics Committee of the HULR (HULR_2022_56). 3. Results 3.1. Descriptive Analysis We obtained a total sample of 2676 women and divided them into two groups: infected with SARS-CoV-2 (n= 52) and uninfected with SARS-CoV-2 (n= 2624). The mean maternal age was 31.2 ± 6.1 years; of the women, 55.5% were nulliparous ( n= 1484 ), and 71.8% were born in Spain (n= 1922). SARS-CoV-2 positivity was determined via RT-PCR (n= 50) and antigen testing (n= 2). The incidence of SARS-CoV-2 infection was 14.6 per 1000 births (18/1236) in 2020 and 23.6 per 1000 births (34/1440) in 2021. A total of 20.5% of the sample was vaccinated (n= 550): 16.5% with a complete Pfizer regimen (n= 442) and 4.0% with at least one dose (n= 108). The median number of days from the last vaccine administration to infection was 102.5 days with an interquartile range of 72.75 days. From the beginning of 2021, SARS-CoV-2 surveillance in Spain included genomic information assessment for confirmation of the presence of variants using sequencing techniques. The information available in the surveillance system in Spain (SiViEs) is analyzed on a weekly basis. This study collected all cases recorded during the first five waves in Spain. According to the SiViEs data, the first three waves (from March 2020 to January 2021) were caused by the alpha variant, the fourth wave (from July to September 2021) by the delta variant, and the fifth wave (from January 2022) by the omicron variant. Thus, the distribution of cases according to the estimation of SARS-CoV-2 variants was as follows: alpha, 38.5% (20/52); delta, 7.7% (4/52); and omicron, 53.8% (28/52). 3.2. Bivariate Analysis Table 1shows the results of the bivariate analysis between the infected and noninfected groups. In total, 1.9% of the sample (n= 52) was positive for SARS-CoV-2. We observed that the risk of infection of unvaccinated women was four times lower compared to vaccinated women (OR: 4.0 (95% CI: 2.3–6.9; p< 0.001). In contrast, when grouping the sample in women vaccinated with a complete regimen (two doses) and incomplete regimen (one dose), the risk estimate suggests that women with incomplete vaccination had five-fold risk compared with those vaccinated with the complete dose (OR: 5.6, 95% CI: 2.2–13.0; p< 0.001). Multiparous women were significantly more infected than nulliparous women (OR: 1.9 95% CI: 1.1–3.3; p= 0.03). Healthcare 2023,11, 2833 7 of 18 Table 1. Comparison of the vaccination status and sociodemographic characteristics between the women non-infected and infected to SARS-CoV-2 (N = 2676). SARS-CoV-2 Infection Total No Yes OR 195% CI 1p-Value *,‡ N = 2676 n= 2624 (98.1%) n= 52 (1.9%) Maternal age 1.00 1.0, 1.0 0.911 Mean (SD) 31.19 (6.12) 31.19 (6.11) 31.29 (6.58) Median (IQR) 32.00 (27.00, 36.00) 32.00 (27.00, 36.00) 31.50 (27.00, 35.25) Range 14.00, 50.00 14.00, 50.00 18.00, 46.00 Parity Primiparous 1484 (55.5%) 1463 (55.8%) 21 (40.4%) 1.00 — Multiparous 1192 (44.5%) 1161 (44.2%) 31 (59.6%) 1.91 1.1, 3.3 0.03 Country of origin Spain 1922 (72%) 1886 (72%) 36 (69%) 1.00 — Foreign 754 (28%) 738 (28%) 16 (31%) 1.13 0.6, 2.0 0.675 Vaccination status No 2126 (79.5%) 2100 (80%) 26 (50%) 1.00 — Yes 550 (20.5%) 524 (20%) 26 (50%) 4.04 2.3, 6.9 <0.001 Dose Unvaccinated 2126 (79%) 2100 (80%) 26 (50%) 1.00 — Incomplete regimen 108 (4.0%) 101 (3.8%) 7 (13%) 5.63 2.2, 13.0 <0.001 Complete regimen 442 (17%) 423 (16%) 19 (37%) 3.64 2.0, 6.6 <0.001 1OR = odds ratio, CI = confidence interval; * Chi-squared test; ‡Student t-test. The sociodemographic variables did not significantly differ between the groups. Table 2shows the comparison of the obstetric variables and their exposure to SARSCoV-2. The data indicate that infected women had a lower risk of developing PROM compared with non-infected women (OR: 0.4 95% CI: 0.2–0.7; p= 0.004). Only 7.7% (4/52) of the women positive for SARS-CoV-2 presented minimal symptoms and, therefore, no antepartum or postpartum complications. The cesarean section rate was 19.7% (527/2676) among the total population, 15.4% (8/52) among the infected group, and 19.8% (519/2624) among the non-infected group; no significant differences were found between the groups. No cases were observed of fetal growth restriction, placental abruption, maternal death, maternal intubation, and cardiac, neurological, thrombotic, and coagulopathy manifestations. We observed that infected women were admitted to ICU for more days (p< 0.001). On the other hand, we analyzed the differences among various maternal comorbidities, such as maternal obesity (BMI > 30 kg/m 2 ), asthma, hyperthyroidism, hypothyroidism, and smoking, and did not observe statistically significant differences between infected and non-infected women. The outcomes and complications in the newborns born to mothers with COVID-19 did not also significantly differ between the groups (Table 3). No cases of neonatal death, neonatal anemia, neonatal sepsis, neonatal SARS-CoV-2 infection, Apgar < 7 at 5 min, and hypoxic ischemic encephalopathy were observed in infected women. Newborns born to infected mothers did have a higher likelihood of NICU admission compared to those born to uninfected mothers (p= 0.014) and a length of stay at NICU more than four days (p= 0.004). Healthcare 2023,11, 2833 8 of 18 Table 2. Comparison of the obstetric characteristics between the non-infected and infected women with SARS-CoV-2 (N = 2676). SARS-CoV-2 Infection Total No Yes OR 195% CI 1p-Value *,‡ N = 2676 (100%) n= 2624 (98.1%) n= 52 (1.9%) Preterm birth < 37 weeks No 2466 (92) 2419 (92.2) 47 (90.4) 1.00 — Yes 210 (7.8) 205 (7.8%) 5 (9.6%) 1.29 0.4, 2.9 0.633 Premature rupture of membranes No 1564 (58) 1523 (58) 41 (79) 1.00 — Yes 1112 (42) 1101 (42) 11 (21) 0.41 0.2, 0.7 0.004 Antepartum hemorrhage No 2651 (99) 2600 (99.1) 51 (98.1) 1.0 — Yes 25 (0.9) 24 (0.9) 1 (1.9) 2.12 0.1, 10 0.465 Postpartum hemorrhage No 2655 (99.2) 2604 (99.2) 51 (98.1) 1.00 — Yes 21 (0.8) 20 (0.8) 1 (1.9) 2.64 0.1, 13 0.365 Caesarean section No 2149 (79.3) 2105 (80.2) 44 (84.6) 1.00 — Yes 527 (19.7) 519 (19.8) 8 (15.4) 0.72 0.3, 1.5 0.432 Instrumental delivery No 2358 (88) 2316 (88) 42 (81) 1.00 — Yes 318 (12) 308 (12) 10 (19) 1.81 0.8, 3.5 0.103 Fetal distress No 2642 (99) 2592 (98.8) 50 (96.2) 1.00 — Yes 34 (1.3) 32 (1.2) 2 (3.8) 3.23 0.5, 11 0.113 Preeclampsia/eclampsia/gestational hypertension/HELLP No 2595 (97) 2544 (97) 51 (98.1) 1.00 — Yes 81 (3.0) 80 (3.0) 1 (1.9) 0.61 0.0, 2.9 0.642 Gestational diabetes No 2479 (93) 2431 (92.6) 48 (92.3) 1.00 — Yes 197 (7.4) 193 (7.4) 4 (7.7) 1.00 0.3, 2.6 0.927 Presence of SARS-CoV-2 signs/symptoms No 2672 (99.9) 2624 (100) 48 (92.3) Yes 4 (0.1) 0 (0) 4 (7.7) ICU admission No 2661 (99.4) 2610 (99.5) 51 (98.1) 1.00 — Yes 15 (0.6) 14 (0.5) 1 (1.9) 3.72 0.2, 19 0.215 Days in ICU Mean (SD) 1.33 (0.90) 1.14 (0.53) 4.00 (NA) Median (IQR) 1.00 (1.00, 1.50) 1.00 (1.00, 1.00) 4.00 (4.00, 4.00) Range 0.00, 4.00 0.00, 2.00 4.00, 4.00 Supplemental oxygen No 2669 (100%) 2618 (99.8%) 51 (98.1%) 1.00 — Yes 7 (0.3%) 6 (0.2%) 1 (1.9%) 8.61 0.4, 51 0.049 Asthma No 2644 (98.8) 2594 (98.9) 50 (96,2) 1.00 — Yes 32 (1.2) 30 (1.1) 2 (3.8) 1.19 0.8, 1.7 0.075 Healthcare 2023,11, 2833 9 of 18 Table 2. Cont. SARS-CoV-2 Infection Total No Yes OR 195% CI 1p-Value *,‡ N = 2676 (100%) n= 2624 (98.1%) n= 52 (1.9%) BMI > 30 kg/m2 No 2418 (90.4) 2370 (90.3) 47 (90.4) 1.00 — Yes 259 (9.6) 254 (9.7) 5 (9.6) 1.21 0.8, 1.3 0.987 Hyperthyroidism No 2632 (98.4) 2581 (98.4) 51 (98.1) 1.00 — Yes 44 (1.6) 43 (1.6) 1 (1.9) 0.17 0.3, 0.6 0.875 Hypothyroidism No 2249 (84.0) 2205 (84.0) 44 (84.6) 1.00 — Yes 427 (26.0) 419 (26.0) 8 (5.4) 0.10 0, 0.3 0.909 Smoker No 2479 (92.6) 2431 (92.6) 48 (92.3) 1.00 — Yes 197 (7.4) 193 (7.4) 4 (7.7) 1.09 0.7, 1.3 0.876 1 OR = odds ratio, CI = confidence interval; * Chi-squared test; ‡ Student t-test; PROM: premature rupture of membranes; ICU: intensive care unit; BMI: body mass index. Table 3. Comparison of neonatal characteristics between non-infected and infected mothers’ newborns to SARS-CoV-2 (N = 2676). SARS-CoV-2 Infection Total No Yes OR 195% CI 1p-Value *,‡ N = 2676 (100%) n= 2624 (98.1%) n= 52 (1.9%) Small for gestational age No 2600 (97.2%) 2550 (97.2%) 50 (96.2%) 1.00 — Yes 76 (2.8%) 74 (2.8%) 2 (3.8%) 1.39 0.2, 4.6 0.661 Large for gestational age No 2354 (88%) 2306 (88%) 48 (92.3%) 1.00 — Yes 322 (12%) 318 (12%) 4 (7.7%) 0.61 0.2, 1.5 0.336 Respiratory distress No 2637 (98.5%) 2587 (98.6%) 50 (96.4%) 1.00 — Yes 39 (1.5%) 37 (1.4%) 2 (3.8%) 2.83 0.4, 9.5 0.165 NICU admission No 2465 (92.1%) 2422 (92.3%) 43 (83%) 1.00 — Yes 211 (7.9%) 202 (7.7%) 9 (17%) 2.47 1.1, 5.0 0.014 Length of stay >4 days No 2647 (98.9%) 2598 (99.0%) 49 (94%) 1.00 — Yes 29 (1.1%) 26 (1.0%) 3 (5.8%) 6.07 1.4, 18 0.004 Ventilator support No 2639 (98.6%) 2589 (98.7%) 50 (96%) 1.00 — Yes 37 (1.4%) 35 (1.3%) 2 (3.8%) 3.00 0.5, 10 0.143 Neonatal death No 2670 (99.8%) 2618 (99.8%) 52 (100%) 1.00 — Yes 6 (0.2%) 6 (0.2%) 0 (0%) 0.00 0.984 1 OR = odds ratio, CI = confidence interval; * Chi-squared test; ‡ Student t-test; NICU: neonatal intensive care unit. 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