Next Article in Journal
Serum Uric Acid but Not Ferritin Level Is Associated with Hepatic Fibrosis in Lean Subjects with Metabolic Dysfunction-Associated Fatty Liver Disease: A Community-Based Study
Previous Article in Journal
Molecular Pathways of Breast Cancer in Systemic Sclerosis: Exploratory Immunohistochemical Analysis from the Sclero-Breast Study
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
JPM
Volume 12
Issue 12
10.3390/jpm12122008
jpm-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19

by
Alicia Martínez-Varea
1,*,
Elena Satorres
1,
Sandra Florez
1,
Josep Domenech
2,
Julia Desco-Blay
1,
Sagrario Monfort-Pitarch
1,
María Hueso
1,
Alfredo Perales-Marín
1 and
Vicente Diago-Almela
1
1
Department of Obstetrics and Gynaecology, La Fe University and Polytechnic Hospital, Avenida Fernando Abril Martorell 106, 46026 Valencia, Spain
2
Department of Economics and Social Sciences, Universitat Politècnica de València, Camí de Vera s/n, 46022 Valencia, Spain
*
Author to whom correspondence should be addressed.
J. Pers. Med. 2022, 12(12), 2008; https://doi.org/10.3390/jpm12122008
Submission received: 28 October 2022 / Revised: 22 November 2022 / Accepted: 2 December 2022 / Published: 3 December 2022
(This article belongs to the Section Epidemiology)
Browse Figures
Versions Notes

Abstract

:
Background: This study sought to elucidate whether COVID-19 vaccination, during gestation or before conception, entails a decreased incidence of severe COVID-19 disease during pregnancy. Methods: This retrospective cohort study included all pregnant women that were followed up at a tertiary University Hospital with SARS-CoV-2 infection diagnosed between 1 March 2020 and 30 July 2022. The primary outcome of the study was to compare maternal and perinatal outcomes in unvaccinated and vaccinated pregnant patients with SARS-CoV-2 infection. Results: A total of 487 pregnant women with SARS-CoV-2 infection were included. SARS-CoV-2 infection during the third trimester of pregnancy was associated with an 89% lower probability of positive cord-blood SARS-CoV-2 IgG antibodies (OR 0.112; 95% CI 0.039–0.316), compared with infection during the first or the second trimester. Vaccinated pregnant women (201 (41.27%)) with COVID-19 had an 80% lower risk for developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients (aOR 0.209; 95% CI 0.044–0.985). Noticeably, pregnant patients with SARS-CoV-2 infection with at least two doses of the COVID-19 vaccine did not develop severe COVID-19. Conclusion: Vaccinated women with SARS-CoV-2 infection during pregnancy are associated with decreased hospital admission due to COVID-19 as well as reduced progression to severe COVID-19.

1. Introduction

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in Wuhan, China, in December 2019 [1]. Due to its notably contagious behavior [2], over 629 million people have been infected, and over 6,5 million have died worldwide as of 27 October 2022 [3]. Mainly transmitted through respiratory droplets [4], the novel coronavirus leads to fever, cough [4,5], and pneumonia [4,6].
Coronavirus Disease 2019 [7] during pregnancy is associated with an increased risk of severe disease [8,9,10] as well as pregnancy complications [8,9,11]. Indeed, compared with nonpregnant women with COVID-19, pregnant patients are more prone to require admission into the intensive care unit (ICU) [10,12,13,14], oxygen therapy [13], invasive ventilation [10,12,13,14], and extracorporeal membrane oxygenation [12] and are more susceptible to death [12,14]. Moreover, particularly severe COVID-19 during pregnancy is associated with low birthweight [15], preterm birth [8,14,15,16,17,18], preeclampsia [8,15,16,19], and stillbirth [8,15,16,17]. Thus, COVID-19 vaccination has been strongly recommended for pregnant women to protect mothers [9,10,20,21] and infants [9,22]. Preliminary data are reassuring regarding the safety of the COVID-19 vaccine for pregnant and lactating women [10,17,21,23,24,25,26]. Recent reports reveal that COVID-19 vaccines are not associated with detrimental consequences on pregnancy outcomes [7,20,21,23,27,28,29]. Nonetheless, data are still limited. Additionally, studies are scant concerning the effectiveness and immune response of COVID-19 vaccines on pregnant women [10,17] and the transfer of IgG antibodies to fetuses [10,26]. Hence, this study sought to elucidate whether COVID-19 vaccination, during gestation or before conception, entails a decreased incidence of severe COVID-19 disease during pregnancy and pregnancy complications associated with COVID-19.

2. Materials and Methods

2.1. Study Design and Participants

This retrospective cohort study included all pregnant women that were followed up at the tertiary University and Polytechnic Hospital La Fe (Valencia, Spain) with SARS-CoV-2 infection diagnosed between 1 March 2020 and 30 July 2022. Patients were included if the diagnosis of SARS-CoV-2 infection was performed during pregnancy. Women were excluded from the study if they had an ongoing pregnancy as of 30 July 2022, were lost to follow-up, or were aged below 18 years of age.
The diagnosis of SARS-CoV-2 infection was based on a positive result on real-time reverse-transcription polymerase chain reaction (RT-PCR) assay [5] or rapid antigen test [30] of nasopharyngeal swab specimens. Pregnant women were tested at the hospital or at the outpatient clinics due to symptoms of, or exposure to, the virus at the time of triage. All pregnant women admitted to the hospital during the study period were also tested. Moreover, pregnant women who reported a positive rapid antigen test performed at home or at the pharmacy because of symptoms of, or exposure to, the SARS-CoV-2 were also included in the study. Neonates of pregnant women who were positive for SARS-CoV-2 during pregnancy or at the time of the delivery were tested with RT-PCR or cord-blood SARS-CoV-2 immunoglobulin G (IgG) and IgM antibodies within 24 hours after delivery.
Data regarding COVID-19 infection during pregnancy, history of COVID-19 vaccination, and maternal and perinatal outcomes were collected from the digital clinical history of the hospital. All medical records were anonymized. Ethical approval for the study was obtained from the Ethical Committee of the Health Research Institute Hospital La Fe (IIS La Fe).

2.2. Outcomes

The outcomes of the study were, firstly, to compare maternal and perinatal outcomes of pregnant patients with asymptomatic and symptomatic SARS-CoV-2 infection. Secondly, to compare maternal and perinatal outcomes in unvaccinated and vaccinated pregnant patients with SARS-CoV-2 infection. Finally, to analyze the severity of COVID-19 disease among pregnant women according to the different SARS-CoV-2 variants and vaccination status.
Symptomatic SARS-CoV-2 infection was defined by the presence of symptoms that included fever, cough, dyspnea, and ageusia-anosmia [4,5,6], associated with a positive RT-PCR assay or rapid antigen test. Fever was defined as an axillary temperature of 38 °C or higher. Asymptomatic SARS-CoV-2 infection was determined by the absence of symptoms associated with a positive RT-PCR assay or rapid antigen test. Vaccinated individuals were defined as those who have received at least one dose of COVID-19 vaccine before the SARS-CoV-2 infection. Obesity was defined as a body mass index ≥ 30 kg/m2. Gestational age was established according to the first-trimester ultrasound. Miscarriage was defined as pregnancy loss prior to 22 weeks of gestation and stillbirth as fetal demise at or beyond 22 weeks. Neonatal death was defined as the death of a liveborn infant in the first 28 days postpartum. Small for gestational age (SGA) was defined as an ultrasound-estimated fetal weight between the 10th and the 3rd percentile with normal Doppler [31,32]. Fetal growth restriction (FGR) was determined by an estimated fetal weight below the 3rd percentile or by the combination of an estimated fetal weight below the 10th percentile with a cerebroplacental ratio beneath the 5th percentile or a mean pulsatility index of the uterine arteries above the 95th percentile [32,33]. Chronic hypertension was defined by systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg before pregnancy or before 20 weeks of gestation [34]. Preeclampsia was defined by new-onset hypertension (repeated measurement of systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg) after 20 weeks of pregnancy and the coexistence of one or both of the following new-onset conditions: proteinuria (urine protein:creatinine ratio ≥30 mg/mmol, or albumin:creatinine ratio ≥8 mg/mmol, or ≥1 g/L [2+] on dipstick testing, or 300 mg protein in a 24-hour urine collection), or other maternal organ dysfunction, including renal, liver, neurological, or hematological complications, or uteroplacental dysfunction (such as fetal growth restriction, abnormal umbilical artery Doppler waveform analysis, or stillbirth) [35,36,37,38]. Gestational diabetes mellitus was defined by fasting plasma glucose >126 mg/dL, casual plasma glucose >200 mg/dl, or plasma or serum glucose >140 mg/dl 1 hour after a 50-gram glucose challenge test followed by at least two abnormal glucose values in the three hours and 100-gram oral glucose tolerance test (≥105 mg/dL, 1 hour ≥190 mg/dL, 2 hours ≥165 mg/dL, and 3 hours ≥145 mg/dL) [39,40]. Preterm premature rupture of membranes was defined as spontaneous rupture of the membranes before 37 weeks of gestation [41]. Threatened preterm labor was defined as the presence of uterine contractions and shortening of the uterine cervix [42]. Preterm birth was defined as delivery before 37+0 weeks of gestation [43].
Four different timeframes of variants’ predominance were identified based on the Spanish Ministry of Health data [44]: timeframe 1, when the Pre-alpha variants prevailed, included cases until 2 April 2021; timeframe 2, when the Alpha variant prevailed in Spain, until 6 August 2021; timeframe 3, when the Delta variant was predominant, until 21 December 2021; and, afterward, timeframe 4 included the cases when Omicron was the principal variant in Spain.

2.3. Statistical Analysis

Categorical variables were presented as absolute and relative frequencies. Continuous variables were shown as means and standard deviations. Comparisons between the characteristics of the groups were performed using Student’s t-test or Kruskal–Wallis test for continuous variables and Fisher’s exact testing for categorical variables.
To assess the potential association between the symptoms and the perinatal outcomes, a multivariate logistic regression was performed adjusting for nulliparity, pre-existing chronic diseases, advanced maternal age (≥36 years old), obesity, and smoking habit. A secondary analysis was also performed to determine the vaccination effects on outcomes, considering the same confounders. Another multivariate logistic regression was performed to assess whether the diagnosis of COVID-19 in the third trimester was associated with the presence of cord-blood SARS-CoV-2 IgG antibodies, adjusting for symptoms and vaccination status. Adjusted odds ratios with a 95% confidence interval were calculated. Analyses were performed in R version 4.0.3.

3. Results

A total of 487 pregnant women that were followed up at our institution had COVID-19 during the study period. Characteristics of pregnant patients with symptomatic (n = 287) and asymptomatic (n = 200) SARS-CoV-2 infection were compared. A higher prevalence of pregnant women through in vitro fertilization among symptomatic patients (9.8% versus 3%, p = 0.004) was found. No other statistical differences were found between groups. Additionally, whereas the majority of pregnant women with COVID-19 during the second trimester (149/487 [30.6%]) were symptomatic (38% versus 20%, p < 0.001), a larger proportion of patients who tested positive for SARS-CoV-2 infection during the third trimester of pregnancy (279/487 [57.3%]) were asymptomatic (50.2% versus 67.5%, p < 0.001) (Table 1).
Regarding maternal outcomes of symptomatic and asymptomatic pregnant women with COVID-19, no patients with asymptomatic SARS-CoV-2 infection developed pneumonia, required hospital admission due to COVID-19, needed antibiotics, corticosteroids, antiviral drugs, or oxygen therapy, or had a composite adverse maternal outcome (Table 2). Among the 28/287 pregnant women with symptomatic COVID-19 who developed pneumonia, one was diagnosed with an associated pulmonary embolism. There were no maternal deaths in our cohort. In respect of perinatal outcomes, newborns from pregnant women with symptomatic COVID-19 displayed a decreased proportion of negative cord-blood SARS-CoV-2 IgG antibodies, compared to newborns from asymptomatic patients (26.8% versus 48.8%, p = 0.045). IgM was not detected in any cord-blood sample. Interestingly, only four newborns from pregnant patients with a symptomatic SARS-CoV-2 infection had a positive SARS-CoV-2 RT-PCR within 24 hours after delivery (Table 2). These three pregnant women, two with a singleton pregnancy and one with a twin pregnancy, had COVID-19 at the time of the delivery. Parameters for perinatal outcomes assessed with a multivariable logistic regression were not statistically significant (Table 3).
A logistic regression demonstrated that SARS-CoV-2 infection during the third trimester of pregnancy was associated with an 89% lower probability of a positive cord-blood SARS-CoV-2 IgG antibodies (odds ratio (OR) 0.112; 95% confidence interval (CI) 0.039–0.316), compared with SARS-CoV-2 infection during the first or the second trimester of pregnancy. When controlled for vaccination status and symptoms during SARS-CoV-2 infection, the adjusted odds ratio (aOR) is 0.115, 95% CI 0.040–0.3331 (Figure 1).
Whereas 201/487 (41.27%) pregnant patients received at least one COVID-19 vaccine before the SARS-CoV-19 infection, 286/487 (58.73%) patients were not vaccinated before the diagnosis of COVID-19. A total of 128/201 (63.7%) patients received a COVID-19 vaccine during pregnancy. While 81/128 received the first COVID-19 dose during gestation, 47/128 were vaccinated during pregnancy and before conception. The patients that were only vaccinated before pregnancy were 73/128 (Figure 2). Vaccinated patients prior to COVID-19 had a higher age (33.0 versus 31.2 years, p < 0.001), a larger requirement of assisted reproductive techniques (11.9% versus 4.2%, p = 0.002), particularly in vitro fertilization (10.9% versus 4.2%, p = 0.006), a reduced incidence of SARS-CoV-2 infection during the first trimester (5.5% versus 16.8%, p < 0.001), and a higher incidence of SARS-CoV-19 infection during the second trimester of pregnancy (36.8% versus 26.2%, p = 0.016), compared with the non-vaccinated pregnant women with COVID-19 (Table 4).
In respect of maternal outcomes of vaccinated and non-vaccinated pregnant patients with COVID-19, vaccinated women associated a significantly reduced incidence of pneumonia (2.0% versus 8.4%, p = 0.03), hospital admission due to COVID-19 (2.0% versus 8.0%, p = 0.004), composite adverse maternal outcome (0.5% versus 3.5%, p = 0.031), and necessity of antibiotics (0.5% versus 4.2%, p = 0.019), corticosteroids (0.5% versus 4.5%, p = 0.01), and oxygen therapy (0.5% versus 5.2%, p = 0.003; Table 5). Pregnant patients with SARS-CoV-2 infection with at least two doses of the COVID-19 vaccine did not develop severe COVID-19 (Figure 3 and Figure 4). Perinatal outcomes were not significantly different between vaccinated and unvaccinated pregnant patients with COVID-19 (Table 5). A multivariate logistic regression demonstrated that vaccinated pregnant women with COVID-19 had an 80% lower risk for developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients (aOR 0.209; 95% CI 0.044–0.985). Other parameters concerning perinatal outcomes addressed within the logistic regression model were not statistically significant (Table 6).
Different variants of SARS-CoV-2 were predominant during the study period. In this cohort, all pregnant women with COVID-19 when the Pre-alpha and Alpha strains were predominant in Spain were unvaccinated. Noticeably, unvaccinated pregnant patients with COVID-19 when the Delta strain prevailed in Spain had the highest rate of hospital admission (24.0%) and the highest progression to severe COVID-19 disease (8.0%) compared to patients in the Pre-alpha period (6.6% and 2.2%, respectively), patients when the Alpha strain was predominant (all 7.9% patients who required hospital admission developed severe COVID-19), and unvaccinated patients when the Omicron strain was dominant (4.8% and 2.4%, respectively). Regarding vaccinated patients when Omicron prevailed in Spain, only 1.6% required hospital admission, and none underwent severe COVID-19 disease (Figure 5).

4. Discussion

The main findings of this retrospective cohort study that included 487 pregnant women with COVID-19 include: (1) asymptomatic patients did not develop pneumonia and did not require hospital admission due to COVID-19; (2) SARS-CoV-2 infection during the third trimester of pregnancy was associated with an 89% lower probability of positive cord-blood SARS-CoV-2 IgG antibodies (OR 0.112; 95% CI 0.039–0.316), compared with the infection during the first or the second trimester of pregnancy; (3) vaccinated pregnant women (201 (41.27%)) with COVID-19 had an 80% lower risk for developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients (aOR 0.209; 95% CI 0.044–0.985); (4) pregnant patients with SARS-CoV-2 infection with at least two doses of the COVID-19 vaccine did not develop severe COVID-19; and (5) unvaccinated pregnant patients with COVID-19 when the Delta strain prevailed in Spain had the highest rate of hospital admission (24.0%), compared to unvaccinated patients when other strains were predominant.
It has been described that physiological, immunologic, and mechanical changes during gestation could predispose to COVID-19 [8,45,46]. Nonetheless, data are scarce to conclude whether or not pregnancy raises vulnerability to SARS-CoV-2 [8]. In the present study, asymptomatic pregnant patients with SARS-CoV-2 infection did not develop pneumonia and did not require hospital admission due to COVID-19. These findings are in concordance with those described by the World Association of Perinatal Medicine Working Group on COVID-19, which reported that SARS-CoV-2 infection during gestation was associated with an 11.1% rate of admission into the intensive care unit, which was significantly higher in symptomatic pregnant women [47]. It has also been reported that, compared with asymptomatic pregnant patients with SARS-CoV-2 infection, those with severe disease had an increased risk of perinatal complications, such as hypertensive disorders of pregnancy, preterm birth, and cesarean delivery [48]. The present study did not find significant differences regarding perinatal complications between asymptomatic and symptomatic pregnant patients with SARS-CoV-2 infection. It might be due to the limited sample size or a higher proportion of vaccinated pregnant women. Interestingly, newborns from pregnant women with symptomatic COVID-19 analyzed in the present study displayed a decreased proportion of negative cord-blood SARS-CoV-2 IgG antibodies, compared with newborns from asymptomatic patients (26.8% versus 48.8%, p = 0.045). Nonetheless, a study with a higher sample size has shown that IgG antibodies to SARS-CoV-2 are present in the cord blood of newborns from symptomatic as well as asymptomatic pregnant women with SARS-CoV-2 [49]. These cord-blood antibody concentrations have been correlated with maternal antibody titles [49] and with the duration between infection and delivery [49,50]. In concordance, in the present study, SARS-CoV-2 infection during the third trimester of pregnancy was associated with an 89% lower probability of positive cord-blood SARS-CoV-2 IgG antibodies irrespective of vaccination status and symptoms during SARS-CoV-2 infection. Given that other authors have reported that the titles of anti-Spike antibodies found in cord blood are lower after SARS-CoV-2 infection during gestation than with COVID-19 vaccination in pregnancy [51,52], further studies are required in order to clarify neonatal protection according to the trimester of both SARS-CoV-2 infection and COVID-19 vaccination. In contrast, only four newborns from this cohort of pregnant patients with a symptomatic SARS-CoV-2 infection at the time of delivery had a positive SARS-CoV-2 RT-PCR within 24 hours after delivery. This finding is in concordance with the reportedly infrequent intrauterine SARS-CoV-2 transmission [8].
In this cohort, 41.27% of pregnant women with COVID-19 had received at least one COVID-19 vaccine before SARS-CoV-2 infection. These patients had an 80% lower risk of developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients (aOR 0.209; 95% CI 0.044–0.985). Noticeably, pregnant patients with SARS-CoV-2 infection with at least two doses of the COVID-19 vaccine did not develop severe COVID-19. It has been reported that a significant proportion of pregnant women are reluctant to receive the first COVID-19 vaccination [23,53] or a booster [54] during gestation. Nonetheless, not only does current data show the safety of COVID-19 vaccination during pregnancy [10,17,21,23,24,25,26], but it also shows that it does not entail adverse pregnancy outcomes [7,20,21,23,27,29]. Thus, COVID-19 vaccination has been strongly recommended for pregnant women to protect both mothers [9,10,20,21,55] and infants [9,22]. COVID-19 vaccine types are those using mRNA (Pfizer, Moderna), viral vector (such as J&J Janssen or AstraZeneca), and inactivated [56]. COVID-19 vaccines using mRNA have been the most widely used in pregnant women and are associated with the most extensive accumulated safety data as well as effectiveness against COVID-19 [56]. Therefore, COVID-19 mRNA vaccines have been recommended as the first option for pregnant women [56]. Despite the limited sample size of the present study, pregnant patients with SARS-CoV-2 infection that have previously received two doses of AstraZeneca displayed the highest hospital admission rate due to COVID-19 compared to pregnant patients with SARS-CoV-2 infection that have previously received two COVID-19 vaccines using mRNA or one AstraZeneca and the other using mRNA.
Unvaccinated pregnant patients with COVID-19 when the Delta strain prevailed in Spain had the highest rate of hospital admission (24.0%) and the highest progression to severe COVID-19 disease (8.0%), compared to unvaccinated patients when other strains were predominant. These results are consistent with the previously reported increased severity of COVID-19 in pregnant women during the Delta variant predominance [57,58,59,60]. Moreover, in the present study, the vaccinated pregnant women with SARS-CoV-2 infection when the Delta variant prevailed were associated with decreased hospital admission and disease severity, similar to previous reports [57,61]. Regarding vaccinated patients when Omicron prevailed in Spain, only 1.6% required hospital admission, and none underwent severe COVID-19 disease. These findings concord with the reported decreased disease severity associated with Omicron [57,62,63].
Future studies are required to determine the optimal timing of COVID-19 vaccination during pregnancy for maternal and neonatal benefit [21]. Additionally, further studies are needed in order to confirm whether SARS-CoV-2 infection during the first and the second trimester is associated with a higher vertical transfer of SARS-CoV-2 IgG antibodies, compared with the infection during the third trimester of pregnancy.
The main strength of the present study is the analysis of maternal and perinatal outcomes of all pregnant women with SARS-CoV-2 infection from a tertiary hospital during the study period, regardless of the trimester of diagnosis and pregnancy outcome. The study also compared maternal and perinatal outcomes among vaccinated and unvaccinated pregnant patients with SARS-CoV-2 infection during the different variants of COVID-19 and associated the number and type of COVID-19 vaccines received prior to the infection. Drawbacks of the study include the limited sample size, as well as the restricted number of newborns from pregnant women with COVID-19 that were tested with RT-PCR or cord-blood SARS-CoV-2 IgG and IgM antibodies within 24 hours after delivery. Additionally, the variants of SARS-CoV-2 were established according to the Spanish Ministry of Health data (44) and not by sequencing analysis.

5. Conclusions

Vaccinated pregnant women with SARS-CoV-2 infection display an 80% lower risk of developing pneumonia and requiring hospital admission due to COVID-19 than unvaccinated patients. Pregnant patients with SARS-CoV-2 infection who had previously received at least two doses of the COVID-19 vaccine did not develop severe COVID-19. Hence, this study further encourages COVID-19 vaccination prior to conception or during pregnancy.

Author Contributions

A.M.-V., V.D.-A. and A.P.-M. performed the conceptualization, methodology, and design of the work. A.M.-V. supervised the research work. A.M.-V., S.M.-P., J.D.-B., M.H. and V.D.-A. contributed to the inclusion of patients in the study and the clinical management of the patients. A.M.-V., E.S. and S.F. carried out the investigation through the acquisition of data for the study. J.D. performed the formal analysis. J.D. and A.M.-V. analyzed and interpreted the study’s data. A.M.-V. wrote the original draft. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

This study protocol was reviewed and approved by the Ethics Committee of the Health Research Institute Hospital La Fe (IIS La Fe), approval Ref: 2022-903-1. The code of the protocol is CoVaGest.

Informed Consent Statement

Patient consent was waived due to the retrospective nature of the study.

Data Availability Statement

The data in this study were obtained from the clinical program of the University and Polytechnic Hospital La Fe. Such a dataset may be completely available on request to the corresponding author. The data are not publicly available due to privacy.

Acknowledgments

Authors acknowledge all members of the Department of Obstetrics and Gynaecology of the University and Polytechnic Hospital La Fe (Valencia, Spain) who have provided health care to pregnant patients with SARS-CoV-2 infection. The authors are grateful to Aida Meló, the nurse who highly contributed to the follow-up of the pregnant patients after SARS-CoV-2 infection in the high-risk pregnancy consult.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Zhu, N.; Zhang, D.; Wang, W.; Li, X.; Yang, B.; Song, J.; Zhao, X.; Huang, B.; Shi, W.; Lu, R. A Novel Coronavirus from Patients with Pneumonia in China, 2019. N. Engl. J. Med. 2020, 382, 727–733. [Google Scholar] [CrossRef] [PubMed]
  2. Chan, J.F.; Yuan, S.; Kok, K.H.; To, K.K.; Chu, H.; Yang, J.; Xing, F.; Liu, J.; Yip, C.C.; Poon, R.W. A familial cluster of pneumonia associated with the 2019 novel coronavirus indicating person-to-person transmission: A study of a family cluster. Lancet 2020, 395, 514–523. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  3. Johns Hopkins University. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU) 2020. Available online: https://coronavirus.jhu.edu/map.html (accessed on 15 October 2022).
  4. Rasmussen, S.A.; Smulian, J.C.; Lednicky, J.A.; Wen, T.S.; Jamieson, D.J. Coronavirus Disease 2019 (COVID-19) and pregnancy: What obstetricians need to know. Am. J. Obstet. Gynecol. 2020, 222, 415–426. [Google Scholar] [CrossRef] [PubMed]
  5. Guan, W.J.; Ni, Z.Y.; Hu, Y.; Liang, W.H.; Ou, C.Q.; He, J.X.; Liu, L.; Shan, H.; Lei, C.L.; Hui, D.S.C. Clinical Characteristics of Coronavirus Disease 2019 in China. N. Engl. J. Med. 2020, 382, 1708–1720. [Google Scholar] [CrossRef]
  6. Yan, J.; Guo, J.; Fan, C.; Juan, J.; Yu, X.; Li, J.; Feng, L.; Li, C.; Chen, H.; Qiao, Y. Coronavirus disease 2019 in pregnant women: A report based on 116 cases. Am. J. Obstet. Gynecol. 2020, 223, 111.e1–111.e14. [Google Scholar] [CrossRef]
  7. Shimabukuro, T.T.; Kim, S.Y.; Myers, T.R.; Moro, P.L.; Oduyebo, T.; Panagiotakopoulos, L.; Marquez, P.L.; Olson, C.K.; Liu, R.; Chang, K.T. Preliminary Findings of mRNA COVID-19 Vaccine Safety in Pregnant Persons. N. Engl. J. Med. 2021, 384, 2273–2282. [Google Scholar] [CrossRef]
  8. Jamieson, D.J.; Rasmussen, S.A. An update on COVID-19 and pregnancy. Am. J. Obstet. Gynecol. 2022, 226, 177–186. [Google Scholar] [CrossRef]
  9. Rasmussen, S.A.; Jamieson, D.J. COVID-19 Vaccination during Pregnancy—Two for the Price of One. N. Engl. J. Med. 2022, 387, 178–179. [Google Scholar] [CrossRef]
  10. Safadi, M.A.P.; Spinardi, J.; Swerdlow, D.; Srivastava, A. COVID-19 disease and vaccination in pregnant and lactating women. Am. J. Reprod. Immunol. 2022, 88, e13550. [Google Scholar] [CrossRef]
  11. Villar, J.; Ariff, S.; Gunier, R.B.; Thiruvengadam, R.; Rauch, S.; Kholin, A.; Roggero, P.; Prefumo, F.; Vale, M.S.d.; Cardona-Perez, J.A. Maternal and Neonatal Morbidity and Mortality Among Pregnant Women With and Without COVID-19 Infection: The INTERCOVID Multinational Cohort Study. JAMA Pediatr. 2021, 175, 817–826. [Google Scholar] [CrossRef]
  12. Zambrano, L.D.; Ellington, S.; Strid, P.; Galang, R.R.; Oduyebo, T.; Tong, V.T.; Woodworth, K.R.; Nahabedian, J.F., III; Azziz-Baumgartner, E.; Gilboa, S.M. Update: Characteristics of Symptomatic Women of Reproductive Age with Laboratory-Confirmed SARS-CoV-2 Infection by Pregnancy Status—United States, January 22–October 3, 2020. MMWR Morb. Mortal. Wkly. Rep. 2020, 69, 1641–1647. [Google Scholar] [CrossRef] [PubMed]
  13. Badr, D.A.; Mattern, J.; Carlin, A.; Cordier, A.; Maillart, E.; el Hachem, L.; el Kenz, H.; Andronikof, M.; de Bels, D.; Damoisel, C. Are clinical outcomes worse for pregnant women at ≥20 weeks’ gestation infected with coronavirus disease 2019? A multicenter case-control study with propensity score matching. Am. J. Obstet. Gynecol. 2020, 223, 764–768. [Google Scholar] [CrossRef] [PubMed]
  14. Allotey, J.; Stallings, E.; Bonet, M.; Yap, M.; Chatterjee, S.; Kew, T.; Zhou, D.; Coomar, D.; Sheikh, J.; Lawson, H. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: Living systematic review and meta-analysis. BMJ 2020, 370, m3320. [Google Scholar] [CrossRef] [PubMed]
  15. Wei, S.Q.; Bilodeau-Bertrand, M.; Liu, S.; Auger, N. The impact of COVID-19 on pregnancy outcomes: A systematic review and meta-analysis. CMAJ 2021, 193, E540–E548. [Google Scholar] [CrossRef]
  16. Di Mascio, D.; Khalil, A.; Saccone, G.; Rizzo, G.; Buca, D.; Liberati, M.; Vecchiet, J.; Nappi, L.; Scambia, G.; Berghella, V. Outcome of Coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: A systematic review and meta-analysis. Am. J. Obstet. Gynecol. MFM 2020, 2, 100107. [Google Scholar] [CrossRef]
  17. Male, V. SARS-CoV-2 infection and COVID-19 vaccination in pregnancy. Nat. Rev. Immunol. 2022, 22, 277–282. [Google Scholar] [CrossRef]
  18. Khalil, A.; Kalafat, E.; Benlioglu, C.; O’Brien, P.; Morris, E.; Draycott, T.; Thangaratinam, S.; Le Doare, K.; Heath, P.; Ladhani, S. SARS-CoV-2 infection in pregnancy: A systematic review and meta-analysis of clinical features and pregnancy outcomes. EClinicalMedicine 2020, 25, 100446. [Google Scholar] [CrossRef]
  19. Papageorghiou, A.T.; Deruelle, P.; Gunier, R.B.; Rauch, S.; García-May, P.K.; Mhatre, M.; Usman, M.A.; Abd-Elsalam, S.; Etuk, S.; Simmons, L.E. Preeclampsia and COVID-19: Results from the INTERCOVID prospective longitudinal study. Am. J. Obstet. Gynecol. 2021, 225, 289.e1–289.e17. [Google Scholar] [CrossRef]
  20. Trostle, M.E.; Limaye, M.A.; Avtushka, V.; Lighter, J.L.; Penfield, C.A.; Roman, A.S. COVID-19 vaccination in pregnancy: Early experience from a single institution. Am. J. Obstet. Gynecol. MFM 2021, 3, 100464. [Google Scholar] [CrossRef]
  21. Badell, M.L.; Dude, C.M.; Rasmussen, S.A.; Jamieson, D.J. COVID-19 vaccination in pregnancy. BMJ 2022, 378, e069741. [Google Scholar] [CrossRef]
  22. Beharier, O.; Mayo, R.P.; Raz, T.; Sacks, K.N.; Schreiber, L.; Suissa-Cohen, Y.; Chen, R.; Gomez-Tolub, R.; Hadar, E.; Gabbay-Benziv, R.; et al. Efficient maternal to neonatal transfer of antibodies against SARS-CoV-2 and BNT162b2 mRNA COVID-19 vaccine. J. Clin. Investig. 2021, 131, e150319. [Google Scholar] [CrossRef] [PubMed]
  23. Blakeway, H.; Prasad, S.; Kalafat, E.; Heath, P.T.; Ladhani, S.N.; Le Doare, K.; Magee, L.A.; O’Brien, P.; Rezvani, A.; von Dadelszen, P.; et al. COVID-19 vaccination during pregnancy: Coverage and safety. Am. J. Obstet. Gynecol. 2022, 226, 236.e1–236.e14. [Google Scholar] [CrossRef] [PubMed]
  24. DeSilva, M.; Haapala, J.; Vazquez-Benitez, G.; Vesco, K.K.; Daley, M.F.; Getahun, D.; Zerbo, O.; Naleway, A.; Nelson, J.C.; Williams, J.T.; et al. Evaluation of Acute Adverse Events after COVID-19 Vaccination during Pregnancy. N. Engl. J. Med. 2022, 387, 187–189. [Google Scholar] [CrossRef] [PubMed]
  25. Bookstein Peretz, S.; Regev, N.; Novick, L.; Nachshol, M.; Goffer, E.; Ben-David, A.; Asraf, K.; Doolman, R.; Gal Levin, E.; Regev Yochay, G.; et al. Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine. Ultrasound Obstet. Gynecol. 2021, 58, 450–456. [Google Scholar] [CrossRef]
  26. Burd, I.; Kino, T.; Segars, J. The Israeli study of Pfizer BNT162b2 vaccine in pregnancy: Considering maternal and neonatal benefits. J. Clin. Investig. 2021, 131, e150790. [Google Scholar] [CrossRef]
  27. Zauche, L.H.; Wallace, B.; Smoots, A.N.; Olson, C.K.; Oduyebo, T.; Kim, S.Y.; Petersen, E.E.; Ju, J.; Beauregard, J.; Wilcox, A.J.; et al. Receipt of mRNA COVID-19 Vaccines and Risk of Spontaneous Abortion. N. Engl. J. Med. 2021, 385, 1533–1535. [Google Scholar] [CrossRef]
  28. Kachikis, A.; Englund, J.A.; Singleton, M.; Covelli, I.; Drake, A.L.; Eckert, L.O. Short-term Reactions Among Pregnant and Lactating Individuals in the First Wave of the COVID-19 Vaccine Rollout. JAMA Netw. Open 2021, 4, e2121310. [Google Scholar] [CrossRef]
  29. Magnus, M.C.; Gjessing, H.K.; Eide, H.N.; Wilcox, A.J.; Fell, D.B.; Håberg, S.E. COVID-19 Vaccination during Pregnancy and First-Trimester Miscarriage. N. Engl. J. Med. 2021, 385, 2008–2010. [Google Scholar] [CrossRef]
  30. Singh, V.; Choudhary, A.; Datta, M.R.; Ray, A. Maternal and Neonatal Outcomes of COVID-19 in Pregnancy: A Single-Centre Observational Study. Cureus 2021, 13, e13184. [Google Scholar] [CrossRef]
  31. Kiserud, T.; Piaggio, G.; Carroli, G.; Widmer, M.; Carvalho, J.; Jensen, L.N.; Giordano, D.; Cecatti, J.G.; Aleem, H.A.; Talegawkar, S.A.; et al. The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight. PLoS Med. 2017, 14, e1002220. [Google Scholar]
  32. Figueras, F.; Gratacós, E. Update on the Diagnosis and Classification of Fetal Growth Restriction and Proposal of a Stage-Based Management Protocol. Fetal Diagn. Ther. 2014, 36, 86–98. [Google Scholar] [CrossRef] [PubMed]
  33. Figueras, F.; Gratacos, E. An integrated approach to fetal growth restriction. Best Pract. Res. Clin. Obstet. Gynaecol. 2017, 38, 48–58. [Google Scholar] [CrossRef]
  34. Seely, E.W.; Ecker, J. Chronic hypertension in pregnancy. Circulation 2014, 129, 1254–1261. [Google Scholar] [CrossRef] [Green Version]
  35. Chaiworapongsa, T.; Chaemsaithong, P.; Yeo, L.; Romero, R. Pre-eclampsia part 1: Current understanding of its pathophysiology. Nat. Rev. Nephrol. 2014, 10, 466–480. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Dröge, L.; Herraìz, I.; Zeisler, H.; Schlembach, D.; Stepan, H.; Küssel, L.; Henrich, W.; Galindo, A.; Verlohren, S. Maternal serum sFlt-1/PlGF ratio in twin pregnancies with and without pre-eclampsia in comparison with singleton pregnancies. Ultrasound Obstet. Gynecol. 2015, 45, 286–293. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Zeisler, H.; Llurba, E.; Chantraine, F.; Vatish, M.; Staff, A.C.; Sennström, M.; Olovsson, M.; Brennecke, S.P.; Stepan, H.; Allegranza, D.; et al. Predictive Value of the sFlt-1:PlGF Ratio in Women with Suspected Preeclampsia. N. Engl. J. Med. 2016, 374, 13–22. [Google Scholar] [CrossRef] [PubMed]
  38. Webster, K.; Fishburn, S.; Maresh, M.; Findlay, S.C.; Chappell, L.C. Diagnosis and management of hypertension in pregnancy: Summary of updated NICE guidance. BMJ 2019, 366, 15119. [Google Scholar] [CrossRef] [PubMed]
  39. American Diabetes Association. Gestational Diabetes Mellitus. Diabetes Care 2003, 26 (Suppl. S1), s103–s105. [Google Scholar] [CrossRef] [Green Version]
  40. Akgöl, E.; Abuşoğlu, S.; Gün, F.D.; Ünlü, A. Prevalence of gestational diabetes mellitus according to the different criterias. J. Turk. Soc. Obstet. Gynecol. 2017, 14, 18–22. [Google Scholar] [CrossRef]
  41. Goldenberg, R.L.; Culhane, J.F.; Iams, J.D.; Romero, R. Epidemiology and causes of preterm birth. Lancet 2008, 371, 75–84. [Google Scholar] [CrossRef]
  42. Cobo, T.; Aldecoa, V.; Bartha, J.L.; Bugatto, F.; Carrillo-Badillo, M.P.; Comas, C.; Diago-Almeda, V.; Ferrero, S.; Goya, M.; Herraiz, I.; et al. Assessment of an intervention to optimise antenatal management of women admitted with preterm labour and intact membranes using amniocentesis-based predictive risk models: Study protocol for a randomised controlled trial (OPTIM-PTL Study). BMJ Open 2021, 11, e054711. [Google Scholar] [CrossRef] [PubMed]
  43. Baños, N.; Julià, C.; Lorente, N.; Ferrero, S.; Cobo, T.; Gratacos, E.; Palacio, M. Mid-Trimester Cervical Consistency Index and Cervical Length to Predict Spontaneous Preterm Birth in a High-Risk Population. Am. J. Perinatol. Rep. 2018, 8, e43–e50. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. SARS-CoV-2 Variants in Spain. [Internet]. 2022. Available online: https://www.sanidad.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/variantes.htm (accessed on 23 October 2022).
  45. Poon, L.C.; Yang, H.; Kapur, A.; Melamed, N.; Dao, B.; Divakar, H.; McIntyre, H.D.; Kihara, A.B.; Ayres-De-Campos, D.; Ferrazzi, E.M.; et al. Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: Information for healthcare professionals. Int. J. Gynecol. Obstet. 2020, 149, 273–286. [Google Scholar] [CrossRef] [PubMed]
  46. Poon, L.C.; Yang, H.; Dumont, S.; Lee, J.C.S.; Copel, J.A.; Danneels, L.; Wright, A.; Costa, F.D.S.; Leung, T.Y.; Zhang, Y.; et al. ISUOG Interim Guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium: Information for healthcare professionals–an update. Ultrasound Obstet. Gynecol. 2020, 55, 848–862. [Google Scholar] [CrossRef]
  47. COVID WWGo. Maternal and perinatal outcomes of pregnant women with SARS-CoV-2 infection. Ultrasound Obstet. Gynecol. 2021, 57, 232–241. [Google Scholar] [CrossRef]
  48. Metz, T.D.; Clifton, R.G.; Hughes, B.L.; Sandoval, G.; Saade, G.R.; Grobman, W.A.; Manuck, T.A.; Miodovnik, M.; Sowles, A.; Clark, K.; et al. Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19). Obstet. Gynecol. 2021, 137, 571–580. [Google Scholar] [CrossRef]
  49. Flannery, D.D.; Gouma, S.; Dhudasia, M.B.; Mukhopadhyay, S.; Pfeifer, M.R.; Woodford, E.C.; Triebwasser, J.E.; Gerber, J.S.; Morris, J.S.; Weirick, M.E.; et al. Assessment of Maternal and Neonatal Cord Blood SARS-CoV-2 Antibodies and Placental Transfer Ratios. JAMA Pediatr. 2021, 175, 594–600. [Google Scholar] [CrossRef]
  50. Song, D.; Prahl, M.; Gaw, S.L.; Narasimhan, S.R.; Rai, D.S.; Huang, A.; Flores, C.V.; Lin, C.Y.; Jigmeddagva, U.; Alan Wu, A.; et al. Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study. BMJ Open 2021, 11, e053036. [Google Scholar] [CrossRef]
  51. Collier, A.-R.Y.; McMahan, K.; Yu, J.; Tostanoski, L.H.; Aguayo, R.; Ansel, J.; Chandrashekar, A.; Patel, S.; Bondzie, E.A.; Sellers, D.; et al. Immunogenicity of COVID-19 mRNA Vaccines in Pregnant and Lactating Women. JAMA 2021, 325, 2370. [Google Scholar] [CrossRef]
  52. Shook, L.L.; Atyeo, C.G.; Yonker, L.M.; Fasano, A.; Gray, K.J.; Alter, G.; Edlow, A.G. Durability of Anti-Spike Antibodies in Infants After Maternal COVID-19 Vaccination or Natural Infection. JAMA 2022, 327, 1087–1089. [Google Scholar] [CrossRef]
  53. Shamshirsaz, A.A.; Hessami, K.; Morain, S.; Afshar, Y.; Nassr, A.A.; Arian, S.E.; Asl, N.M.; Aagaard, K. Intention to Receive COVID-19 Vaccine during Pregnancy: A Systematic Review and Meta-analysis. Am. J. Perinatol. 2021, 39, 492–500. [Google Scholar] [CrossRef] [PubMed]
  54. Abbasi, J. COVID-19 mRNA Vaccine Booster During Pregnancy Increases Maternal and Fetal Antibodies. JAMA 2022, 328, 120. [Google Scholar] [CrossRef] [PubMed]
  55. Stafford, I.A.; Parchem, J.G.; Sibai, B.M. The coronavirus disease 2019 vaccine in pregnancy: Risks, benefits, and recommendations. Am. J. Obstet. Gynecol. 2021, 224, 484–495. [Google Scholar] [CrossRef]
  56. Kalafat, E.; Heath, P.; Prasad, S.; O Brien, P.; Khalil, A. COVID-19 vaccination in pregnancy. Am. J. Obstet. Gynecol. 2022, 227, 136–147. [Google Scholar] [CrossRef]
  57. Eid, J.; Abdelwahab, M.; Williams, H.; Caplan, M.; Hajmurad, S.; Venkatesh, K.K.; Costantine, M.M.; Rood, K.M. Decreased severity of COVID-19 in vaccinated pregnant individuals during predominance of different SARS-CoV-2 variants. Am. J. Reprod. Immunol. 2022, 88, e13596. [Google Scholar] [CrossRef] [PubMed]
  58. Adhikari, E.H.; SoRelle, J.A.; McIntire, D.D.; Spong, C.Y. Increasing severity of COVID-19 in pregnancy with Delta (B.1.617.2) variant surge. Am. J. Obstet. Gynecol. 2021, 226, 149–151. [Google Scholar] [CrossRef] [PubMed]
  59. Seasely, A.R.; Blanchard, C.T.; Arora, N.; Battarbee, A.N.; Casey, B.M.; Dionne-Odom, J.; Sixto, M., Jr.; Moates, D.B.; Sinkey, R.G.; Szychowski, J.M.; et al. Maternal and Perinatal Outcomes Associated with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) Variant. Obstet. Gynecol. 2021, 138, 842–844. [Google Scholar] [CrossRef] [PubMed]
  60. Wang, A.M.; Berry, M.; Moutos, C.P.; Omere, C.; Clark, S.M.; Harirah, H.M.; Jain, S.; Olson, G.L.; Pacheco, L.D.; Saade, G.R.; et al. Association of the Delta (B.1.617.2) Variant of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) with Pregnancy Outcomes. Obstet. Gynecol. 2021, 138, 838–841. [Google Scholar] [CrossRef]
  61. Morgan, J.A.; Biggio, J.R., Jr.; Martin, J.K.; Mussarat, N.; Chawla, H.K.; Puri, P.; Williams, F.B. Maternal Outcomes After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Vaccinated Compared with Unvaccinated Pregnant Patients. Obstet. Gynecol. 2022, 139, 107–109. [Google Scholar] [CrossRef]
  62. Adhikari, E.H.; MacDonald, L.; SoRelle, J.A.; Morse, J.; Pruszynski, J.; Spong, C.Y. COVID-19 Cases and Disease Severity in Pregnancy and Neonatal Positivity Associated with Delta (B.1.617.2) and Omicron (B.1.1.529) Variant Predominance. JAMA 2022, 327, 1500. [Google Scholar] [CrossRef]
  63. Ilter, P.B.; Prasad, S.; Berkkan, M.; Mutlu, M.A.; Tekin, A.B.; Celik, E.; Ata, B.; Turgal, M.; Yildiz, S.; Turkgeldi, E.; et al. Clinical severity of SARS-CoV-2 infection among vaccinated and unvaccinated pregnancies during the Omicron wave. Ultrasound Obstet. Gynecol. 2022, 59, 560–562. [Google Scholar] [CrossRef] [PubMed]
Jpm 12 02008 g001 550
Figure 1. Cord-blood SARS-CoV-2 IgG antibody seropositivity of newborns from pregnant women with SARS-CoV-2 infection during the indicated trimester of pregnancy.
Figure 1. Cord-blood SARS-CoV-2 IgG antibody seropositivity of newborns from pregnant women with SARS-CoV-2 infection during the indicated trimester of pregnancy.
Jpm 12 02008 g001
Jpm 12 02008 g002 550
Figure 2. Timing of COVID-19 vaccination in the pregnant patients (201/487 (41.27%)) who received at least one COVID-19 vaccine before the SARS-CoV-19 infection. The number of patients that received the first, second, or third dose of a vaccine before or during the different trimesters of pregnancy is shown.
Figure 2. Timing of COVID-19 vaccination in the pregnant patients (201/487 (41.27%)) who received at least one COVID-19 vaccine before the SARS-CoV-19 infection. The number of patients that received the first, second, or third dose of a vaccine before or during the different trimesters of pregnancy is shown.
Jpm 12 02008 g002
Jpm 12 02008 g003 550
Figure 3. Progression to severe COVID-19 among vaccinated pregnant women with SARS-CoV-2 infection according to the number of doses of COVID-19 vaccine. Severe COVID-19 was defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation.
Figure 3. Progression to severe COVID-19 among vaccinated pregnant women with SARS-CoV-2 infection according to the number of doses of COVID-19 vaccine. Severe COVID-19 was defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation.
Jpm 12 02008 g003
Jpm 12 02008 g004 550
Figure 4. Progression to severe COVID-19 among vaccinated pregnant women with SARS-CoV-2 infection according to the number of doses and type of COVID-19 vaccine. Severe COVID-19 was defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation.
Figure 4. Progression to severe COVID-19 among vaccinated pregnant women with SARS-CoV-2 infection according to the number of doses and type of COVID-19 vaccine. Severe COVID-19 was defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation.
Jpm 12 02008 g004
Jpm 12 02008 g005 550
Figure 5. Progression to severe COVID-19 among vaccinated pregnant women with SARS-CoV-2 infection according to the SARS-CoV-2 strain predominance and vaccination status. Severe COVID-19 was defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation.
Figure 5. Progression to severe COVID-19 among vaccinated pregnant women with SARS-CoV-2 infection according to the SARS-CoV-2 strain predominance and vaccination status. Severe COVID-19 was defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation.
Jpm 12 02008 g005
Table
Table 1. Pregnant women with SARS-CoV-2 infection, overall and according to the presence of symptoms.
Table 1. Pregnant women with SARS-CoV-2 infection, overall and according to the presence of symptoms.
Total Sample (n = 487)Symptomatic (n = 287)Asymptomatic (n = 200)p
Maternal age (years)32.0 ± 5.532.0 ± 5.731.9 ± 5.30.96
Pre-existing chronic disease *93/486 (19.1 (15.7–22.9))58/286 (20.3 (15.8–25.4))35/200 (17.5 (12.5–23.5))0.483
Smoking habit32/485 (6.6 (4.6–9.2))21/286 (7.3 (4.6–11.0))11/199 (5.5 (2.8–9.7))0.463
Weight (kg)66.4 ± 14.165.7 ± 14.267.4 ± 14.00.213
Obesity **47/338 (13.9 (10.4–18.1))23/200 (11.5 (7.4–16.8))24/138 (17.4 (11.5–24.8))0.15
Nulliparity240/483 (49.7 (45.1–54.2))147/283 (51.9 (46.0–57.9))93/200 (46.5 (39.4–53.7))0.268
Twin pregnancy16/487 (3.3 (1.9–5.3))9/287 (3.1 (1.4–5.9))7/200 (3.5 (1.4–7.1))0.803
Assisted reproductive techniques36/487 (7.4 (5.2–10.1))28/287 (9.8 (6.6–13.8))8/200 (4.0 (1.7–7.7))0.021
Artificial insemination2/487 (0.4 (0.0–1.5))0/287 (0.0 (0.0–1.3))2/200 (1.0 (0.1–3.6))0.168
In vitro fertilization34/487 (7.0 (4.9–9.6))28/287 (9.8 (6.6–13.8))6/200 (3.0 (1.1–6.4))0.004
Egg donation4/487 (0.8 (0.2–2.1))4/287 (1.4 (0.4–3.5))0/200 (0.0 (0.0–1.8))0.148
SARS-CoV-2 infection during 1st trimester59/487 (12.1 (9.4–15.3))34/287 (11.8 (8.3–16.2))25/200 (12.5 (8.3–17.9))0.888
SARS-CoV-2 infection during 2nd trimester149/487 (30.6 (26.5–34.9))109/287 (38.0 (32.3–43.9))40/200 (20.0 (14.7–26.2))<0.001
SARS-CoV-2 infection during 3rd trimester279/487 (57.3 (52.8–61.7))144/287 (50.2 (44.2–56.1))135/200 (67.5 (60.5–73.9))<0.001
Data are given as n/N (%) or mean ± SD. * Including diabetes, chronic hypertension, asthma, autoimmune disease, infection by human immunodeficiency virus, hepatitis B virus, or hepatitis C virus. ** Defined as body mass index ≥ 30 kg/m2.
Table
Table 2. Maternal and perinatal outcomes of 487 pregnancies with SARS-CoV-2 infection, overall and according to the presence of symptoms.
Table 2. Maternal and perinatal outcomes of 487 pregnancies with SARS-CoV-2 infection, overall and according to the presence of symptoms.
Total Sample (n = 487)Symptomatic (n = 287)Asymptomatic (n = 200)p
Maternal outcome
Pneumonia28/487 (5.7 (3.9–8.2))28/287 (9.8 (6.6–13.8))0/200 (0.0 (0.0–1.8))<0.001
Hospital admission due to COVID-1927/487 (5.5 (3.7–8.0))27/287 (9.4 (6.3–13.4))0/200 (0.0 (0.0–1.8))<0.001
Admission into the intensive care unit11/27 (40.7 (22.4–61.2))11/27 (40.7 (22.4–61.2))0/0 (0.0 (0.0–0.0))1.0
Composite adverse maternal outcome *11/487 (2.3 (1.1–4.0))11/287 (3.8 (1.9–6.8))0/200 (0.0 (0.0–1.8))0.004
Antibiotic treatment13/487 (2.7 (1.4–4.5))13/287 (4.5 (2.4–7.6))0/200 (0.0 (0.0–1.8))0.001
Corticosteroid drug14/487 (2.9 (1.6–4.8))14/287 (4.9 (2.7–8.0))0/200 (0.0 (0.0–1.8))<0.001
Antiviral drug10/487 (2.1 (1.0–3.7))10/287 (3.5 (1.7–6.3))0/200 (0.0 (0.0–1.8))0.007
Oxygen therapy16/487 (3.3 (1.9–5.3))16/287 (5.6 (3.2–8.9))0/200 (0.0 (0.0–1.8))<0.001
Intubation7/487 (1.4 (0.6–2.9))7/287 (2.4 (1.0–5.0))0/200 (0.0 (0.0–1.8))0.045
Extracorporeal membrane oxygenation1/487 (0.2 (0.0–1.1))1/287 (0.3 (0.0–1.9))0/200 (0.0 (0.0–1.8))1.0
Perinatal outcome
Ectopic pregnancy1/487 (0.2 (0.0–1.1))0/287 (0.0 (0.0–1.3))1/200 (0.5 (0.0–2.8))0.411
Miscarriage9/487 (1.8 (0.8–3.5))4/287 (1.4 (0.4–3.5))5/200 (2.5 (0.8–5.7))0.498
Stillbirth2/487 (0.4 (0.0–1.5))1/287 (0.3 (0.0–1.9))1/200 (0.5 (0.0–2.8))1.0
Completed pregnancies (excluding ectopic pregnancy and miscarriage)
Threatened preterm labor5/477 (1.0 (0.3–2.4))3/283 (1.1 (0.2–3.1))2/194 (1.0 (0.1–3.7))1.0
Small for gestational age4/477 (0.8 (0.2–2.1))1/283 (0.4 (0.0–2.0))3/194 (1.5 (0.3–4.5))0.309
Fetal growth restriction16/477 (3.4 (1.9–5.4))10/283 (3.5 (1.7–6.4))6/194 (3.1 (1.1–6.6))1.0
Gestational diabetes mellitus30/477 (6.3 (4.3–8.9))21/283 (7.4 (4.7–11.1))9/194 (4.6 (2.1–8.6))0.253
Gestational hypertension6/477 (1.3 (0.5–2.7))1/283 (0.4 (0.0–2.0))5/194 (2.6 (0.8–5.9))0.043
Preeclampsia4/477 (0.8 (0.2–2.1))2/283 (0.7 (0.1–2.5))2/194 (1.0 (0.1–3.7))1.0
Preterm premature rupture of membranes3/477 (0.6 (0.1–1.8))1/283 (0.4 (0.0–2.0))2/194 (1.0 (0.1–3.7))0.569
Gestational age at delivery (weeks)39.2 ± 1.739.2 ± 1.839.1 ± 1.60.168
Cesarean section121/477 (25.4 (21.5–29.5))74/283 (26.1 (21.1–31.7))47/194 (24.2 (18.4–30.9))0.669
Preterm birth38/475 (8.0 (5.7–10.8))20/282 (7.1 (4.4–10.7))18/193 (9.3 (5.6–14.3))0.393
Singleton pregnancy
Gestational age at delivery (weeks)39.3 ± 1.739.3 ± 1.839.2 ± 1.50.187
Preterm birth29/459 (6.3 (4.3–8.9))16/273 (5.9 (3.4–9.3))13/186 (7.0 (3.8–11.7))0.697
Birth weight (g)3254.2 ± 480.63263.3 ± 500.43240.9 ± 451.00.483
1 min Apgar 9.2 ± 1.19.2 ± 1.09.2 ± 1.20.717
5 min Apgar9.9 ± 0.59.9 ± 0.59.9 ± 0.40.602
5 min Apgar < 72/458 (0.4 (0.1–1.6))2/273 (0.7 (0.1–2.6))0/185 (0.0 (0.0–2.0))0.517
Umbilical artery pH7.2 ± 0.17.2 ± 0.17.3 ± 0.10.202
Umbilical artery pH < 7.16/447 (1.3 (0.5–2.9))3/269 (1.1 (0.2–3.2))3/178 (1.7 (0.3–4.8))0.686
Umbilical venous pH7.3 ± 0.17.3 ± 0.17.3 ± 0.10.254
Neonatal morbidity **43/459 (9.4 (6.9–12.4))28/273 (10.3 (6.9–14.5))15/186 (8.1 (4.6–13.0))0.515
Neonatal death1/459 (0.2 (0.0–1.2))1/273 (0.4 (0.0–2.0))0/186 (0.0 (0.0–2.0))1.0
Positive RT-PCR SARS-CoV-22/122 (1.6 (0.2–5.8))0/48 (0.0 (0.0–7.4))2/74 (2.7 (0.3–9.4))0.519
Positive cord-blood SARS-CoV-2 immunoglobulin G antibodies52/84 (61.9 (50.7–72.3))30/41 (73.2 (57.1–85.8))22/43 (51.2 (35.5–66.7))0.045
Twin pregnancy
Gestational age at delivery (weeks)36.4 ± 0.936.7 ± 0.936.0 ± 0.90.135
Preterm birth9/16 (56.3 (29.9–80.2))4/9 (44.4 (13.7–78.8))5/7 (71.4 (29.0–96.3))0.358
Birth weight (g) of the first twin2408.6 ± 363.02441.7 ± 364.22366.0 ± 385.80.874
Birth weight (g) of the second twin2402.5 ± 332.82389.4 ± 374.62419.3 ± 298.80.634
1 min Apgar of the first twin9.4 ± 0.99.6 ± 0.79.1 ± 1.10.373
1 min Apgar of the second twin8.9 ± 1.28.9 ± 1.38.9 ± 1.20.912
5 min Apgar of the first twin9.7 ± 0.89.8 ± 0.49.6 ± 1.10.816
5 min Apgar of the second twin9.8 ± 0.49.9 ± 0.39.7 ± 0.50.39
5 min Apgar < 7 of the first twin0/16 (0.0 (0.0–20.6))0/9 (0.0 (0.0–33.6))0/7 (0.0 (0.0–41.0))1.0
5 min Apgar < 7 of the second twin0/16 (0.0 (0.0–20.6))0/9 (0.0 (0.0–33.6))0/7 (0.0 (0.0–41.0))1.0
Umbilical artery pH of the first twin7.3 ± 0.17.3 ± 0.07.2 ± 0.00.002
Umbilical artery pH of the second twin7.3 ± 0.17.3 ± 0.07.2 ± 0.10.345
Umbilical artery pH < 7.1 of the first twin0/15 (0.0 (0.0–21.8))0/9 (0.0 (0.0–33.6))0/6 (0.0 (0.0–45.9))1.0
Umbilical artery pH < 7.1 of the second twin0/15 (0.0 (0.0–21.8))0/9 (0.0 (0.0–33.6))0/6 (0.0 (0.0–45.9))1.0
Umbilical venous pH of the first twin7.3 ± 0.17.3 ± 0.07.3 ± 0.10.022
Umbilical venous pH of the second twin7.3 ± 0.17.3 ± 0.07.3 ± 0.10.123
Neonatal morbidity ** of the first twin2/16 (12.5 (1.6–38.3))0/9 (0.0 (0.0–33.6))2/7 (28.6 (3.7–71.0))0.175
Neonatal morbidity ** of the second twin2/16 (12.5 (1.6–38.3))1/9 (11.1 (0.3–48.2))1/7 (14.3 (0.4–57.9))1.0
Neonatal death0/16 (0.0 (0.0–20.6))0/9 (0.0 (0.0–33.6))0/7 (0.0 (0.0–41.0))1.0
Positive RT-PCR SARS-CoV-2, first twin1/6 (16.7 (0.4–64.1))0/2 (0.0 (0.0–84.2))1/4 (25.0 (0.6–80.6))1.0
Positive RT-PCR SARS-CoV-2, second twin1/3 (33.3 (0.8–90.6))0/0 (0.0 (0.0–0.0))1/3 (33.3 (0.8–90.6))1.0
Positive cord-blood SARS-CoV-2 immunoglobulin G antibodies, first twin1/5 (20.0 (0.5–71.6))0/2 (0.0 (0.0–84.2))1/3 (33.3 (0.8–90.6))1.0
Positive cord-blood SARS-CoV-2 immunoglobulin G antibodies, second twin2/3 (66.7 (9.4–99.2))1/1 (100.0 (2.5–100.0))1/2 (50.0 (1.3–98.7))1.0
Data are given as n/N (% (95% CI)) or mean ± SD. * Defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation. ** Including sepsis of unknown origin, neonatal jaundice, anemia, congenital anomalies, neonatal thrombocytopenia, and others.
Table
Table 3. Odds ratios (ORs), adjusted odds ratios (aORs), and 95% confidence intervals (CIs) for perinatal outcomes among the symptomatic and asymptomatic pregnant patients with SARS-CoV-2 infection.
Table 3. Odds ratios (ORs), adjusted odds ratios (aORs), and 95% confidence intervals (CIs) for perinatal outcomes among the symptomatic and asymptomatic pregnant patients with SARS-CoV-2 infection.
VariableOR (95% CI)aOR (95% CI)
Preterm birth 0.742 (0.382–1.443)0.745 (0.313–1.776)
Fetal growth restriction1.148 (0.410–3.212)0.904 (0.245–3.340)
Preeclampsia0.683 (0.095–4.892)1.204 (0.103–14.074)
Stillbirth0.696 (0.043–11.190)0.925 (0.054–15.962)
Cesarean section1.107 (0.726–1.689)1.060 (0.630–1.782)
Umbilical artery pH < 7.11.519 (0.303–7.611)1.217 (0.158–9.357)
Neonatal morbidity *1.141 (0.606–2.148)0.914 (0.447–1.868)
aOR adjusted for nulliparity, pre-existing chronic diseases, maternal age > 36 years old, obesity, and smoking habit. * Including sepsis of unknown origin, neonatal jaundice, anemia, congenital anomalies, neonatal thrombocytopenia, and others.
Table
Table 4. Characteristics of 487 pregnant women with SARS-CoV-2 infection, overall and according to the vaccination status.
Table 4. Characteristics of 487 pregnant women with SARS-CoV-2 infection, overall and according to the vaccination status.
Total Sample (n = 487)Vaccinated (n = 201)Not Vaccinated (n = 286)p
Maternal age (years)32.0 ± 5.533.0 ± 4.931.2 ± 5.8<0.001
Pre-existing chronic disease *93/486 (19.1 (15.7–22.9))44/201 (21.9 (16.4–28.3))49/285 (17.2 (13.0–22.1))0.2
Smoking habit32/485 (6.6 (4.6–9.2))12/199 (6.0 (3.2–10.3))20/286 (7.0 (4.3–10.6))0.714
Weight (kg)66.4 ± 14.165.3 ± 13.667.4 ± 14.50.118
Obesity **47/338 (13.9 (10.4–18.1))19/159 (11.9 (7.4–18.0))28/179 (15.6 (10.7–21.8))0.349
Nulliparity240/483 (49.7 (45.1–54.2))105/198 (53.0 (45.8–60.1))135/285 (47.4 (41.5–53.3))0.23
Twin pregnancy16/487 (3.3 (1.9–5.3))5/201 (2.5 (0.8–5.7))11/286 (3.8 (1.9–6.8))0.452
Assisted reproductive techniques36/487 (7.4 (5.2–10.1))24/201 (11.9 (7.8–17.2))12/286 (4.2 (2.2–7.2))0.002
Artificial insemination2/487 (0.4 (0.0–1.5))2/201 (1.0 (0.1–3.5))0/286 (0.0 (0.0–1.3))0.17
In vitro fertilization34/487 (7.0 (4.9–9.6))22/201 (10.9 (7.0–16.1))12/286 (4.2 (2.2–7.2))0.006
Egg donation4/487 (0.8 (0.2–2.1))3/201 (1.5 (0.3–4.3))1/286 (0.3 (0.0–1.9))0.311
SARS-CoV-2 infection during 1st trimester59/487 (12.1 (9.4–15.3))11/201 (5.5 (2.8–9.6))48/286 (16.8 (12.6–21.6))<0.001
SARS-CoV-2 infection during 2nd trimester149/487 (30.6 (26.5–34.9))74/201 (36.8 (30.1–43.9))75/286 (26.2 (21.2–31.7))0.016
SARS-CoV-2 infection during 3rd trimester279/487 (57.3 (52.8–61.7))116/201 (57.7 (50.6–64.6))163/286 (57.0 (51.0–62.8))0.926
Symptomatic SARS-CoV-2 infection287/487 (58.9 (54.4–63.3))125/201 (62.2 (55.1–68.9))162/286 (56.6 (50.7–62.5))0.226
Data are given as n/N (%) or mean ± SD. * Including diabetes, chronic hypertension, asthma, autoimmune disease, infection by human immunodeficiency virus, hepatitis B virus, or hepatitis C virus. ** Defined as body mass index ≥ 30 kg/m2.
Table
Table 5. Maternal and perinatal outcomes of 487 pregnancies with SARS-CoV-2 infection, overall and according to the vaccination status.
Table 5. Maternal and perinatal outcomes of 487 pregnancies with SARS-CoV-2 infection, overall and according to the vaccination status.
Total Sample (n = 487)Vaccinated (n = 201)Not Vaccinated (n = 286)p
Maternal outcome
Pneumonia28/487 (5.7 (3.9–8.2))4/201 (2.0 (0.5–5.0))24/286 (8.4 (5.5–12.2))0.003
Hospital admission due to SARS-CoV-2 infection27/487 (5.5 (3.7–8.0))4/201 (2.0 (0.5–5.0))23/286 (8.0 (5.2–11.8))0.004
Admission into the intensive care unit11/27 (40.7 (22.4–61.2))1/4 (25.0 (0.6–80.6))10/23 (43.5 (23.2–65.5))0.624
Composite adverse maternal outcome *11/487 (2.3 (1.1–4.0))1/201 (0.5 (0.0–2.7))10/286 (3.5 (1.7–6.3))0.031
Antibiotic treatment13/487 (2.7 (1.4–4.5))1/201 (0.5 (0.0–2.7))12/286 (4.2 (2.2–7.2))0.019
Corticosteroid drug14/487 (2.9 (1.6–4.8))1/201 (0.5 (0.0–2.7))13/286 (4.5 (2.4–7.6))0.01
Antiviral drug10/487 (2.1 (1.0–3.7))1/201 (0.5 (0.0–2.7))9/286 (3.1 (1.4–5.9))0.052
Oxygen therapy16/487 (3.3 (1.9–5.3))1/201 (0.5 (0.0–2.7))15/286 (5.2 (3.0–8.5))0.003
Intubation7/487 (1.4 (0.6–2.9))1/201 (0.5 (0.0–2.7))6/286 (2.1 (0.8–4.5))0.248
Extracorporeal membrane oxygenation1/487 (0.2 (0.0–1.1))0/201 (0.0 (0.0–1.8))1/286 (0.3 (0.0–1.9))1.0
Perinatal outcome
Ectopic pregnancy1/487 (0.2 (0.0–1.1))0/201 (0.0 (0.0–1.8))1/286 (0.3 (0.0–1.9))1.0
Miscarriage9/487 (1.8 (0.8–3.5))3/201 (1.5 (0.3–4.3))6/286 (2.1 (0.8–4.5))0.742
Stillbirth2/487 (0.4 (0.0–1.5))2/201 (1.0 (0.1–3.5))0/286 (0.0 (0.0–1.3))0.17
Completed pregnancies (excluding ectopic pregnancy and miscarriage)
Threatened preterm labor5/477 (1.0 (0.3–2.4))2/198 (1.0 (0.1–3.6))3/279 (1.1 (0.2–3.1))1.0
Small for gestational age4/477 (0.8 (0.2–2.1))4/198 (2.0 (0.6–5.1))0/279 (0.0 (0.0–1.3))0.029
Fetal growth restriction16/477 (3.4 (1.9–5.4))6/198 (3.0 (1.1–6.5))10/279 (3.6 (1.7–6.5))0.802
Gestational diabetes mellitus30/477 (6.3 (4.3–8.9))11/198 (5.6 (2.8–9.7))19/279 (6.8 (4.1–10.4))0.703
Gestational hypertension6/477 (1.3 (0.5–2.7))1/198 (0.5 (0.0–2.8))5/279 (1.8 (0.6–4.1))0.408
Preeclampsia4/477 (0.8 (0.2–2.1))1/198 (0.5 (0.0–2.8))3/279 (1.1 (0.2–3.1))0.645
Preterm premature rupture of membranes3/477 (0.6 (0.1–1.8))2/198 (1.0 (0.1–3.6))1/279 (0.4 (0.0–2.0))0.573
Gestational age at delivery (weeks)39.2 ± 1.739.2 ± 1.639.2 ± 1.80.507
Cesarean section121/477 (25.4 (21.5–29.5))59/198 (29.8 (23.5–36.7))62/279 (22.2 (17.5–27.6))0.07
Preterm birth38/475 (8.0 (5.7–10.8))13/196 (6.6 (3.6–11.1))25/279 (9.0 (5.9–12.9))0.395
Singleton pregnancy
Gestational age at delivery (weeks)39.3 ± 1.739.3 ± 1.639.3 ± 1.80.343
Preterm birth29/459 (6.3 (4.3–8.9))11/191 (5.8 (2.9–10.1))18/268 (6.7 (4.0–10.4))0.846
Birth weight (g)3254.2 ± 480.63236.3 ± 424.23267.0 ± 517.50.308
1 min Apgar 9.2 ± 1.19.2 ± 0.99.2 ± 1.20.349
5 min Apgar9.9 ± 0.59.9 ± 0.59.9 ± 0.50.04
5 min Apgar < 72/458 (0.4 (0.1–1.6))1/190 (0.5 (0.0–2.9))1/268 (0.4 (0.0–2.1))1.0
Umbilical artery pH7.2 ± 0.17.2 ± 0.17.2 ± 0.10.976
Umbilical artery pH < 7.16/447 (1.3 (0.5–2.9))3/186 (1.6 (0.3–4.6))3/261 (1.1 (0.2–3.3))0.697
Umbilical venous pH7.3 ± 0.17.3 ± 0.17.3 ± 0.10.23
Neonatal morbidity **43/459 (9.4 (6.9–12.4))25/191 (13.1 (8.7–18.7))18/268 (6.7 (4.0–10.4))0.023
Neonatal death1/459 (0.2 (0.0–1.2))0/191 (0.0 (0.0–1.9))1/268 (0.4 (0.0–2.1))1.0
Positive RT-PCR SARS-CoV-22/122 (1.6 (0.2–5.8))0/28 (0.0 (0.0–12.3))2/94 (2.1 (0.3–7.5))1.0
Positive cord-blood SARS-CoV-2 immunoglobulin G antibodies52/84 (61.9 (50.7–72.3))1/1 (100.0 (2.5–100.0))51/83 (61.4 (50.1–71.9))1.0
Twin pregnancy
Gestational age at delivery (weeks)36.4 ± 0.936.6 ± 0.636.3 ± 1.00.278
Preterm birth9/16 (56.3 (29.9–80.2))2/5 (40.0 (5.3–85.3))7/11 (63.6 (30.8–89.1))0.596
Birth weight (g) of the first twin2408.6 ± 363.02398.0 ± 352.82413.4 ± 384.40.777
Birth weight (g) of the second twin2402.5 ± 332.82339.0 ± 309.32431.4 ± 353.50.61
1 min Apgar of the first twin9.4 ± 0.99.4 ± 0.99.4 ± 0.90.949
1 min Apgar of the second twin8.9 ± 1.27.8 ± 1.39.4 ± 0.80.021
5 min Apgar of the first twin9.7 ± 0.89.6 ± 0.59.7 ± 0.90.212
5 min Apgar of the second twin9.8 ± 0.49.6 ± 0.59.9 ± 0.30.155
5 min Apgar < 7 of the first twin0/16 (0.0 (0.0–20.6))0/5 (0.0 (0.0–52.2))0/11 (0.0 (0.0–28.5))1.0
5 min Apgar < 7 of the second twin0/16 (0.0 (0.0–20.6))0/5 (0.0 (0.0–52.2))0/11 (0.0 (0.0–28.5))1.0
Umbilical artery pH of the first twin7.3 ± 0.17.3 ± 0.07.3 ± 0.10.387
Umbilical artery pH of the second twin7.3 ± 0.17.3 ± 0.17.3 ± 0.00.713
Umbilical artery pH < 7.1 of the first twin0/15 (0.0 (0.0–21.8))0/5 (0.0 (0.0–52.2))0/10 (0.0 (0.0–30.8))1.0
Umbilical artery pH < 7.1 of the second twin0/15 (0.0 (0.0–21.8))0/5 (0.0 (0.0–52.2))0/10 (0.0 (0.0–30.8))1.0
Umbilical venous pH of the first twin7.3 ± 0.17.3 ± 0.07.3 ± 0.10.776
Umbilical venous pH of the second twin7.3 ± 0.17.3 ± 0.17.3 ± 0.10.776
Neonatal morbidity ** of the first twin2/16 (12.5 (1.6–38.3))1/5 (20.0 (0.5–71.6))1/11 (9.1 (0.2–41.3))1.0
Neonatal morbidity ** of the second twin2/16 (12.5 (1.6–38.3))0/5 (0.0 (0.0–52.2))2/11 (18.2 (2.3–51.8))1.0
Neonatal death0/16 (0.0 (0.0–20.6))0/5 (0.0 (0.0–52.2))0/11 (0.0 (0.0–28.5))1.0
Positive RT-PCR SARS-CoV-2, first twin1/6 (16.7 (0.4–64.1))0/0 (0.0 (0.0–0.0))1/6 (16.7 (0.4–64.1))1.0
Positive RT-PCR SARS-CoV-2, second twin1/3 (33.3 (0.8–90.6))0/0 (0.0 (0.0–0.0))1/3 (33.3 (0.8–90.6))1.0
Positive cord-blood SARS-CoV-2 immunoglobulin G antibodies, first twin1/5 (20.0 (0.5–71.6))0/0 (0.0 (0.0–0.0))1/5 (20.0 (0.5–71.6))1.0
Positive cord-blood SARS-CoV-2 immunoglobulin G antibodies, second twin2/3 (66.7 (9.4–99.2))0/0 (0.0 (0.0–0.0))2/3 (66.7 (9.4–99.2))1.0
Data are given as n/N (% (95% CI)) or mean ± SD. * Defined as at least one of the following: admission to the intensive care unit, intubation, or extracorporeal membrane oxygenation. ** Including sepsis of unknown origin, neonatal jaundice, anemia, congenital anomalies, neonatal thrombocytopenia, and others.
Table
Table 6. Odds ratios (ORs), adjusted odds ratios (aORs), and 95% confidence intervals (CIs) for perinatal outcomes among the vaccinated and unvaccinated pregnant women with SARS-CoV-2 infection.
Table 6. Odds ratios (ORs), adjusted odds ratios (aORs), and 95% confidence intervals (CIs) for perinatal outcomes among the vaccinated and unvaccinated pregnant women with SARS-CoV-2 infection.
VariableOR (95% CI)aOR (95% CI)
Pneumonia0.222 (0.076–0.649)0.209 (0.044–0.985)
Hospital admission due to COVID-190.232 (0.079–0.682)0.209 (0.044–0.985)
Preterm birth0.722 (0.360–1.449)1.024 (0.433–2.424)
Fetal growth restriction0.841 (0.300–2.352)1.047 (0.289–3.787)
Preeclampsia0.467 (0.048–4.523)0.517 (0.045–5.940)
Cesarean section1.486 (0.981–2.250)1.200 (0.723–1.993)
Umbilical artery pH < 7.10.701 (0.140–3.513)0.893 (0.120–6.626)
Neonatal morbidity *2.093 (1.123–3.900)1.982 (0.957–4.103)
aOR adjusted for nulliparity, pre-existing chronic diseases, maternal age > 36 years old, obesity, and smoking habit. * Including sepsis of unknown origin, neonatal jaundice, anemia, congenital anomalies, neonatal thrombocytopenia, and others.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

Martínez-Varea, A.; Satorres, E.; Florez, S.; Domenech, J.; Desco-Blay, J.; Monfort-Pitarch, S.; Hueso, M.; Perales-Marín, A.; Diago-Almela, V. Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19. J. Pers. Med. 2022, 12, 2008. https://doi.org/10.3390/jpm12122008

AMA Style

Martínez-Varea A, Satorres E, Florez S, Domenech J, Desco-Blay J, Monfort-Pitarch S, Hueso M, Perales-Marín A, Diago-Almela V. Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19. Journal of Personalized Medicine. 2022; 12(12):2008. https://doi.org/10.3390/jpm12122008

Chicago/Turabian Style

Martínez-Varea, Alicia, Elena Satorres, Sandra Florez, Josep Domenech, Julia Desco-Blay, Sagrario Monfort-Pitarch, María Hueso, Alfredo Perales-Marín, and Vicente Diago-Almela. 2022. "Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19" Journal of Personalized Medicine 12, no. 12: 2008. https://doi.org/10.3390/jpm12122008

APA Style

Martínez-Varea, A., Satorres, E., Florez, S., Domenech, J., Desco-Blay, J., Monfort-Pitarch, S., Hueso, M., Perales-Marín, A., & Diago-Almela, V. (2022). Comparison of Maternal–Fetal Outcomes among Unvaccinated and Vaccinated Pregnant Women with COVID-19. Journal of Personalized Medicine, 12(12), 2008. https://doi.org/10.3390/jpm12122008

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop