The impact of SARS-CoV-2 infection on vaccinated versus unvaccinated pregnant women: a retrospective cohort study

Abstract

Background/Objectives

Pregnant women were included in the COVID-19 vaccination strategy adopted in Spain in May 2021. We evaluated the obstetric and neonatal symptoms and complications presented by these first pregnant women infected with SARS-CoV-2, vaccinated and unvaccinated.

Methods

A retrospective observational cohort study of 156 pregnant women with a positive diagnosis of SARS-CoV-2 (infection rate of 4.2%, 156/3719 births), treated at two public hospitals in the Valencian Community (Spain) over two years (2020–2022). Of those pregnant women infected, 28.8% (45) had received at least one dose of the COVID-19 vaccine before infection. The data were obtained from the digital medical record, the Nominal Vaccination Registry (RNV), and symptom data from the Epidemiological Surveillance Application (AVE) of the CV, supervised by the epidemiology units. We analyzed the symptoms of the disease and the main obstetric and neonatal variables depending on whether or not they were vaccinated with mRNA vaccines.

Results

Most pregnant women were diagnosed in the third trimester of pregnancy (p = 0.003) and reported symptoms associated with the infection (73%), but vaccinated women reported all the symptoms described to a lesser extent, with headache (R1.38, 95%IC 1.15 to 1.66) and vomiting (R 1.38, 95%IC 1.15 to 1.66) statistically significant. All cases of pneumonia occurred in unvaccinated pregnant women who required ventilatory assistance and referral to the Intensive Care Unit. Pregnant women vaccinated against SARS-CoV-2 infection had lower rates of gestational pathology, milder symptoms, and fewer postpartum complications than unvaccinated women, although the small sample size did not allow for a significant difference to be seen. Neonatal outcomes were similar in both groups.

Conclusions

COVID-19 vaccination in pregnant women with at least one dose is associated with reduced symptoms, less headache and vomiting, and fewer maternal complications, including pneumonia, which did not occur in the vaccinated cohort. Furthermore, the Apgar score at one and five minutes is higher than 7 in children of immunized mothers.Public health strategies should promote access to vaccines during pregnancy as an urgent priority, to minimize the risk of complications from COVID-19.

Introduction

On March 11, 2020, the World Health Organization (WHO) declared COVID-19 a pandemic [1] and the first confirmed case of SARS-CoV-2 in Spain was declared on January 31, 2020 [1]. This made it necessary for the European Medicines Agency (EMA) to reinforce the need for vaccines as a preventive measure, with messenger RNA (mRNA) type vaccines being chosen: Pfizer (21 December 2020) and Moderna (6 January 2021), prioritising their administration to different population groups by means of a staggered process [2, 3]. Pregnant women were initially excluded from vaccination, but the increase in the number of cases, new infectious variants and the appearance of clinical complications in both mothers and infants meant that as of May 2021 mRNA vaccination was considered a safe alternative for this population group [2], despite the lack of previous scientific evidence in this group [4]. Pregnant women represented a vulnerable group to the disease, and as such, they had to weigh these documented complications of COVID-19 infection against the unknown safety of vaccination in deciding whether to receive the vaccine [5].

An increase in infection among pregnant women during the fifth epidemic wave of COVID-19 in Spain, between June and September 2021 [3], led to increased vaccination campaigns aimed at this group [6]. Infectious disease mRNA vaccines could be administered concomitantly with other vaccines, at different anatomical sites, including influenza vaccine and diphtheria-tetanus-acellular pertussis (dTpa) vaccine. Additionally, complete vaccination prior to the third trimester of pregnancy was strongly recommended due to increased risk of complications from COVID-19 [7, 8].

The clinical presentation in pregnant women with SARS-CoV-2 infection can be asymptomatic (up to 75% of pregnant women) [9], moderate or severe. However, the disease can affect the course of pregnancy through both maternal and fetal complications. The obstetric complications described include an increased risk of pre-eclampsia, caesarean section, intrauterine growth retardation, premature delivery and even stillbirth [10,11,12,13]. Furthermore, there is a high rate of pneumonia among infected pregnant women and of admission to intensive care units [14, 15]. Evaluating the global impact that COVID-19 has had on pregnant women in a meta-analysis with 13,136 infected women with data from 12 countries, including Spain, it is concluded that this disease can increase the risk of maternal morbidity and mortality and in the infant it almost doubles the probability of being admitted to a neonatal care unit [16].

In clinical trials for the development of the COVID-19 vaccine, several health organizations and institutions recommended its administration during pregnancy due to the double potential benefit [17], first, for the mother, and second for her child through placental transfer of antibodies, as a preventive measure against infant infections during the first months of life [18, 19]. Maternal vaccination generates both humoral and cellular immune responses in the mother, protecting her against infection and thus reducing the risk of transmission to the foetus [19].

In Spain, the Ministry of Health sets specific vaccination recommendations for pregnant and puerperal women, and the monitoring of coverage in the different regions is of public interest [20].

The vaccinations recommended during pregnancy correspond to immunisation against influenza, pertussis and COVID-19. From the 2021–2022 season, vaccination against influenza and COVID-19 overlap.

Current scientific evidence has identified no adverse events during pregnancy associated with prenatal vaccination against COVID-19 [21,22,23,24], and the immunological protection it confers on the mother has been demonstrated [25]. Furthermore, the vaccine confers immunity to the newborn, through the transplacental route and through breast milk, and transmission of SARS-CoV-2 from mother to foetus has not been demonstrated [21]. Vaccination during pregnancy is also associated with a decrease in fetal morbidity and mortality [21].

For all the above reasons, observational epidemiological studies are needed to analyze the impact of the disease and to confirm the hypothetical protection conferred by vaccination in infected pregnant women and newborns. In this study, a two-year retrospective analysis of the clinical evolution of pregnant women infected with SARS-CoV-2 was carried out. Maternal and neonatal events were analyzed among infected pregnant women vaccinated against COVID-19 or not vaccinated belonging to two Health Departments of the Valencian Community (Spain).

Materials and methods

Design, population and sample

A retrospective observational cohort study was conducted based on a review of the digital medical records of all pregnant women diagnosed positive for SARS-CoV-2. The diagnostic result was laboratory confirmed by antigen testing or polymerase chain reaction (PCR) during pregnancy or at the time of delivery.

The study population corresponds to pregnant women who attended and clinically followed up at the Hospital Universitario San Juan de Alicante and the Hospital Marina Baixa (Alicante, Spain) from 1 March 2020 to 31 March 2022. Single and multiple births were included, with follow-up of mothers and their live newborns until hospital discharge. Both hospitals are part of CV health departments that provided care, through the national public health system, to a total of 3719 births during the study period.

There were 45 pregnant women who tested positive for SARS-CoV-2 who received at least one dose of COVID-19 vaccine (vaccinated group), and there were 111 SARS-CoV-2 positive pregnant women who did not receive any dose of COVID-19 vaccine (not vaccinated group).

Inclusion criteria were: (a) being pregnant with a positive result for SARS-CoV-2 infection by taking nasopharyngeal exudate for PCR and/or antigen testing, at some point during pregnancy or during delivery; (b) having undergone pregnancy and delivery monitoring in one of the two participating health departments between March 1, 2020 and March 31, 2022; (c) being over 16 years of age (high obstetric risk pregnancy); (d) having telematic vaccination data in the nominal vaccination register (NVR) and symptomatology data in the CV’s Epidemiological Surveillance Application (ESA). Pregnant women infected with SARS-CoV-2 who delivered at a hospital other than the hospitals participating in the study were excluded from the study. It is important to note that ESA is a tool available in all hospitals in the Valencian Community and that it allows a standardized and controlled registry [26].

If the maternal clinical condition was good, newborns were not separated from their mothers after birth (skin-to-skin technique) and breastfeeding was recommended [25].

For the calculation of the sample size, a 5% margin of error and a confidence interval of 95% were applied, resulting in a minimum sample size required for this study of 131 pregnant women infected with SARS-CoV-2.

Variables

For the acquisition of data related to SARS-CoV-2 infection and symptomatology, the digital medical records of both health departments were consulted during hospital stay and at the time of discharge. The Nominal Vaccine Register (NVR) included in the Computer Application for Epidemiological Surveillance (AES) was consulted to identify the number of vaccination doses received by the pregnant women along with their symptoms. This is an online collection system overseen by the central services and areas and the epidemiology units of the Public Health Centres of the CV. Vaccinated women were defined as those who had received at least one dose of COVID-19 vaccine prior to SARS-CoV-2 infection, and the symptoms were those declared by the patients.

In addition, if the PCR is positive, the cycle threshold (Ct) at which the sample is positive shall be considered to be assessed. The cycle threshold (Ct) is the number of cycles of DNA amplification required for the fluorescent signal to be detected in a gene expression determination by reverse transcriptase polymerase chain reaction (RT-PCR). The lower the cycle threshold level, the greater the amount of RNA (genetic material) in the sample. It is assumed that a Ct < 30 is equivalent to a high viral load, with infectious capacity [27].

Demographic and obstetric data were obtained from the common digital medical record for both Orion Logis ^® departments.

Once the sample was obtained, the variables were classified as: demographic (age and year of delivery); obstetric (gestational age, parity, maternal obstetric history, maternal pathology prior to gestation, current pathology, type of onset of labour, complications during dilation and delivery, type of end of labour, complications during puerperium, maternal destination, dTpa vaccination); neonatal (fetal pathology, fetal outcome, weight, sex, 1 min and 5 min Apgar test, cord arterial pH, neonatal destination, type of infant feeding, skin-to-skin contact after delivery); related to SARS-CoV-2 virus (trimester of pregnancy in which SARS-CoV-2 infection was diagnosed, number of doses received, type of vaccine administered, trimester of gestation in which the vaccine was received and presence of symptoms characteristic of COVID-19).

Methods of analysis

All analyzed variables were categorical, expressed as response counts (percentages) and displayed in frequency tables. Pearson’s Chi-square test was used to determine factors associated with vaccination. The risk of developing COVID-19-associated symptomatology, complications during pregnancy, labour and delivery or during the postpartum period, and neonatal complications among vaccinated and unvaccinated women was shown by indicating the risk (R) with corresponding 95% confidence intervals (CI). Sub-analyses according to the trimester of pregnancy in which women were diagnosed with COVID-19 and according to the number of doses of COVID-19 vaccine received among those vaccinated were conducted. An analysis of the consistency of the missing data and values was performed (Supplementary material, Table S1). Pairwise analysis of available data was carried out. Statistical significance was set at α < 0.05. Analyses were conducted using IBM SPSS Statistics software, version 29.0 (SPSS Inc., Chicago, IL, USA).

Ethical considerations

The study was carried out according to the principles from the Declaration of Helsinki on human clinical trials (Ref No. 579/06/2020) and was approved by the Biomedical Research Ethics Committee of the Cardenal Herrera CEU University (CEEI23/426). As this was a retrospective study, it did not require informed consent from the pregnant women. The anonymity of the participants was guaranteed at all times and each history was coded to preserve the confidentiality of the data. No personal data were collected that would allow the identification of the subject. The data collected were included in a computerized database of a personal nature, to which access was granted only to the researcher responsible for the analysis, by means of an access code, being subject to the secrecy inherent to his profession and derived from a confidentiality agreement.

Results

Demographic data

A total of 156 women gave birth after being confirmed positive for SARS-CoV-2 during their pregnancy. This represents an infection rate of 4.2% (156/3719) of the total number of deliveries attended in the hospitals during the study period. Of the total sample, 45 (28.8%) pregnant women had received at least one dose of the COVID-19 vaccine prior to infection (vaccinated group) and 111 (71.2%) were not vaccinated (Table 1). Among the vaccinated pregnant women, 20 (44.4%) received their first dose in the first trimester, 15 (33.3%) in the second trimester and 4 (8.9%) in the third trimester. Regarding the type of first vaccine received, 30 (66.7%) received BNT162b2 (Pfizer), 11 (24.4%) SPIKEVAX (Moderna) and 4 (8.9%) Vaxzevria (Astrazeneca). Of the women vaccinated against COVID-19, 7 (15.6%) received only one dose, while 38 (84%) received two or more doses of the vaccine.

Table 1 Demographic and COVID-19 diagnosis-related characteristics of pregnant women who participated in the study

Pregnant women aged 16 to 34 years constituted the most representative cohort of those infected with SARS-CoV-2 (Table 1). In terms of year of pregnancy, the majority of unvaccinated women became pregnant in 2020 (65.8%), while the majority of vaccinated women became pregnant in 2021 (95.6%). The proportion of primiparous and multiparous pregnant women was evenly distributed. Most of the vaccinated pregnant women were diagnosed in the third trimester of pregnancy (R:1.45; 95% IC: 1.17–1.79), showing a significant difference compared to the non-vaccinated group (p = 0.003). The estimated viral load was high for most of the pregnant women, showing no significant differences between vaccinated and unvaccinated women. Pregnant women diagnosed in the third trimester showed a higher proportion of high viral load than those diagnosed in the first trimester (p = 0.006). Those diagnosed in the second trimester also showed a higher proportion of high viral load than those diagnosed in the first trimester (p = 0.031).

Of the pregnant women, 47 (30.1%) reported the presence of pathology prior to pregnancy, 62 (39.7%) reported complications in previous pregnancies and 126 (90%) received dTpa vaccination (Table 1). Among the previous pathologies, hypothyroidism (7.1%), obesity (3.2%) or high blood pressure (1.3%) were the most common. Among the complications in previous pregnancies, abortion (17.9%), caesarean delivery (9%), instrumental delivery (5.1%), pre-eclampsia (2.6%), preterm delivery (1.9%), cross-foetus (1.3%) or ectopic delivery (1.3%) were the most common (data not shown).

When comparing between vaccinated and unvaccinated pregnant women, no significant differences were observed in terms of age, parity, presence of previous pathology, previous pregnancy complications, viral load or dTpa vaccination. There were also no significant differences between the vaccinated and unvaccinated groups when analysing each of the previous pathologies or each of the complications in previous pregnancies (data not shown). These results show the homogeneity between the two groups of pregnant women in terms of the variables that define the characteristics of the population, which reduces selection bias and facilitates valid comparisons. (Table 1).

Symptomatology associated with SARS-CoV-2 infection

Symptomatology associated with SARS-Cov-2 infection is shown in Table 2. Of the pregnant women, 73.3% reported symptoms associated with SARS-CoV-2 infection and of these, 72% had not received any vaccine dose. The frequency of symptoms among them, regardless of whether they were vaccinated or not, was: cough (46.3%), dyspnoea (34.6%), anosmia/dysgeusia (33.8%), fever (26.5%), headache (28.7%), myalgia (22.8%), congestion (20.6%), general discomfort (18.4%), coryza (16.2%), sore throat (15.4%), vomiting (9.3%), shaking chills (6.6%) and diarrhoea (5.1%).

Table 2 Symptomatology associated with COVID-19 in vaccinated and unvaccinated pregnant women

When comparing between groups, the majority of symptoms were more frequent among unvaccinated pregnant women than among vaccinated women, although only headache (R1.38, 95%IC 1.15 to 1.66) and vomiting (R 1.38, 95%IC 1.15 to 1.66) showed a significant greater risk among unvaccinated pregnant women (Table 2; Fig. 1). All symptoms were less severe and, in some cases, absent in vaccinated pregnant women compared to unvaccinated women, as shown in Fig. 1. Furthermore, 5 cases of pneumonia were reported, all among unvaccinated women. All cases of pneumonia were diagnosed by their symptoms and after a chest x-ray. The five cases of pneumonia among the unvaccinated were in pregnant women diagnosed in the third trimester.

Fig. 1

Comparison of symptomatology associated with SARS-CoV-2 infection between vaccinated and unvaccinated pregnant women

Analysis of COVID-19-associated symptomatology according to the gestational age at which pregnant women were diagnosed with the infection is shown in Table S2 of the supplementary material. In the third trimester of pregnancy, the unvaccinated women showed greater symptomatology for all symptoms evaluated except coryza, with a significant increase risk in congestion (R 1.27, 95% CI 1.o5 to 1.53) and headache (R 1.36, 95% CI 1.09 to 1.71). As most women were diagnosed in the third trimester, we had to pool women diagnosed in the first and second trimester to make a comparison between vaccinated and unvaccinated pregnant women. The results only show a significant increase in anosmia among unvaccinated women (R 1.64, 95% CI 1.30 to 2.o7). In any case, the sample in this early gestational age comparison was very small.

The symptoms reported in vaccinated pregnant women were also analysed according to the number of vaccination doses received (Fig. 2 and supplementary material Table S3). All pregnant women who received 1 dose reported having symptoms, while only 70% of those who received 2 or more doses reported having symptoms. Pregnant women vaccinated with two or more doses showed a lower risk of having headache (p = 0.048), general discomfort (p = 0.048) and chills (p = 0.048) (Table S3).

Fig. 2

Unreported symptoms in vaccinated pregnant women according to the number of vaccination doses received

Characteristics of childbirth and complications during pregnancy

Birth characteristics and complications during pregnancy are shown in Table 3. The onset of labour was mainly spontaneous or induced, and in most cases, labour ended in spontaneous or induced birth. Of the births, 133 (85.3%) were term, and there were no post-term births. There were 10 (6.4%) miscarriages and ectopic pregnancies (Table 3). Of the pregnant women, 48.4% had complications during gestation: premature rupture of membranes (24.8%), Streptococcus agalactiae positive (14.2%), gestational diabetes (8.4%), hypertensive disease of pregnancy (5.8%), hypothyroidism (4.5%), anaemia (1.9%) or retained placenta (1.3%) (Supplementary material, Table S4). 49.7% had complications during dilation or delivery, including episiotomy (20.5%), risk of loss of fetal well-being (13.8%), meconium amniotic fluid (6.2%), perineal tear (4.5%), HTA (2.1%) or threatened preterm delivery (2.1%) (Supplementary material, Table S4). Complications in the postpartum period affected 37.1% of the pregnant women, including anaemia (28.6%), excessive bleeding (2.7%) or urinary tract infection (1.4%) (Supplementary material, Table S4). However, no significant differences were observed between vaccinated and unvaccinated pregnant women in terms of delivery characteristics or the frequency of any of the complications described during pregnancy, delivery or puerperium (Table 3 and Supplementary material, Table S4). Five pregnant women were diagnosed with pneumonia, two of whom had obesity as a previous comorbidity and one had anemia and hypertensive disease during pregnancy. Three of them required ventilatory support and two were referred to the Intensive Care Unit, all of them belonging to the unvaccinated group.

Table 3 Birth characteristics and complications during pregnancy for vaccinated and unvaccinated pregnant women

When differentiating by trimester of COVID-19 diagnosis, 5 miscarriages (10.4%) were observed among vaccinated women diagnosed in the first or second trimester of pregnancy compared to 1 miscarriage (2.7%) among those diagnosed in the third trimester. This resulted in a higher risk of miscarriage in the group diagnosed in the first or second trimester among vaccinated women (R 18.5, 95% CI 2.38 to 144.2, p < 0.001). Similarly, among unvaccinated women, those diagnosed with COVID-19 in the third trimester showed a lower risk of miscarriage than those diagnosed in the first or second trimester (R 0.89, 95% CIn 0.081 to 0.99, p = 0.009). The remaining characteristics of childbirth and complications during pregnancy showed no significant differences when adjusted for trimester of COVID-19 diagnosis (data not shown).

Newborn characteristics in vaccinated and unvaccinated pregnant women

Characteristics of the neonate are shown in Table 4. Of the newborns, most were of normal weight and male. Most showed normal cord arterial pH results and the Apgar test at 1 min and 5 min was greater than 7. Of the newborns, 16 (10.9%) required admission to intensive care. Most of the newborns were breastfed 124 (86.1%) and had skin-to-skin contact with the mother 120 (82.2%). However, no significant differences were observed for any of the variables defining neonatal characteristics, nor for any of the complications reported between neonates of vaccinated and unvaccinated pregnant women for SARS-Cov-2 (Table 4). When adjusted for trimester of COVID-19 diagnosis, the newborn characteristics of childbirth and complications showed no significant differences (data not shown).

Table 4 Characteristics of the neonate in vaccinated and unvaccinated pregnant women

Discussion

This retrospective cohort study provides new information on the clinical outcomes of pregnant women infected with SARS-CoV-2, as well as the association between COVID-19 during pregnancy and maternal-neonatal outcomes among pregnant women who received a vaccination regimen prior to their diagnosis of the disease compared to those who were not immunised.

Symptomatology in pregnant women infected with SARS-Cov-2

Pregnant patients present similar COVID-19 symptoms to the general population, with the most common period of diagnosis being during the third trimester (n = 100, 56.8% of unvaccinated women and 82.2% of vaccinated women), mainly because they attended via maternity clinic [23, 28]. This is in line with other studies conducted internationally, in the United Kingdom [29], Turkey [30], China [7], as well as similar studies at the national level [31].

Currently, the scientific evidence reviewed suggests that an association exists between a COVID-19-positive pregnant woman and an increased susceptibility to the development of clinical complications [6, 11, 15, 18, 32].

Approximately 63% of the pregnant women presented some symptoms, the most frequently described symptoms being cough (46.3%), dyspnoea (34.6%) anosmia (23.8%) and fever (19%), also coinciding with the findings of other studies [33, 34].

Similarly, it should be noted that in our analysis, vaccinated pregnant women reported fewer symptoms such as headache, vomiting and myalgia, with no cases of pneumonia being diagnosed in this group, results similar to those reported in other studies [28]. However, among unvaccinated pregnant women, one in four infected with COVID-19 was diagnosed with pneumonia, coinciding with the findings of Lokken EM et al. [35]. These data underscore the effectiveness of vaccination in reducing the severity of the disease. The COVID-19 vaccine is known to reduce the severity of symptoms by inducing an adaptive immune response that includes neutralising antibodies, effective T-cells and immunological memory, resulting in lower viral load, shorter disease duration and less likelihood of severe inflammation, both in the general population and in the present risk group [28, 36, 37].

Pregnant women who received two or more doses of the vaccine were also found to have fewer symptoms than those vaccinated with one dose [21, 38] and did not develop severe COVID-19 [29], suggesting a beneficial dose-response effect. In addition, the literature indicates the transplacental transfer of SARS-CoV-2 antibodies after maternal COVID-19 vaccination during the third trimester of pregnancy [28, 38].

The study findings support vaccination as a safe and effective intervention associated with reduced severity of COVID-19 symptoms as well as prevention of serious complications. These results are consistent with the existing literature and show the need for health professionals to prioritise education and motivation strategies among pregnant women to increase the acceptance of vaccination during pregnancy, as well as the implementation of risk assessment protocols adapted to individual characteristics, prioritising intensive monitoring in unvaccinated pregnant women [18, 36].

Adherence to pertussis vaccination is notable, both in pregnant women vaccinated against SARS-CoV-2 and in unvaccinated pregnant women, results that are consistent with data reported in other studies conducted during the pandemic [39], and which, in turn, reinforce the importance and effectiveness of vaccination during pregnancy as a preventive measure, despite this group being excluded from the initial research. This study, along with others, underlines the need for the inclusion of pregnant women in vaccination strategies [18,19,20, 40]. Otherwise, the absence of evidence could lead to this group being excluded from vaccination due to concerns about safety during pregnancy [10, 23, 41].

Obstetric and neonatal complications

The percentage of caesarean sections at the end of labour in our study was 22.3%, in line with the rate of caesarean sections in public hospitals in the CV [42], although vaginal births predominated in the vaccinated group, reaching 85.4% [6].

Although there are no statistically significant differences in disease complications between vaccinated and unvaccinated women, we observed a higher percentage of complications during pregnancy in the unvaccinated group compared to the vaccinated group (52.7% vs. 37.8%), with hypertensive disease of pregnancy [43] and group B streptococcus positive being the complications that showed the greatest difference between the two groups.

Similarly, it should be noted that one of the complications of COVID-19 infection described in the literature is preterm birth, which in our study accounted for 14.7% of the sample, lower than that described in other studies, where it is around 25% [28, 44]. In this study, unvaccinated women gave birth earlier than vaccinated women [15, 45].

Likewise, fetal well-being is represented in this work by the arterial pH data of all newborns and their Apgar assessment at one minute and five minutes.

In the same way, high rates were recorded for aspects such as breastfeeding (86.1%) and skin-to-skin contact (82.2%), in line with the recommendations and benefits for the newborn issued by the Spanish Society of Neonatology in May 2020 [25]. These results coincide with similar studies reported in this area, showing 70.8% breastfeeding and 75.4% skin-to-skin contact [35]. These data are likely influenced by a context of uncertainty, affected by fear of contagion, and need to control the disease.

The newborns had more favourable outcomes for COVID-19 than the mothers. Most newborns are asymptomatic in our study, in line with current research [46, 47].

Therefore, the results of our study confirm the hypothesis that vaccinated pregnant women have lower severity of disease symptoms and fewer maternal complications, indicated by the absence of pneumonia in the vaccinated group. In addition, although neonatal outcomes were similar between groups, higher Apgar scores in infants born to vaccinated women support the hypothesis that vaccination does not compromise neonatal outcomes. These data reinforce vaccination as a safe and effective preventive measure during pregnancy. Two recent systematic reviews identify a reduction in the risk of hospitalization for COVID-19 during pregnancy by 53% [48] and 94% [22], cesarean section was reduced by 9% [22], the risk of admission to the neonatal ICU by 8% and 20%, respectively, in vaccinated pregnant women [22, 48], both studies conclude that vaccination was not associated with increased risk during the perinatal period.

Strengths and limitations

In this study, the cohort size of those vaccinated was modest. The vaccinated group (n = 45) is much smaller than the unvaccinated group (n = 111), which may affect the reliability of statistical comparisons, especially for rare outcomes. However, we included all positive cases managed in the two health departments during the study period without any loss in follow-up and exceeding the estimated sample size for sufficient representation. Although the sample was not stratified by severity among the COVID-positive pregnant women. With respect to data collection from medical records, possible inaccuracy in the quality of reporting of vaccination or symptomatology data was mitigated by checking these data against two other registries, the AES and NVR official registries in the Valencia Region. The concurrent use of the two databases (NVR and AES) improves the validity of the vaccine data. Having all the positive cases in the two hospitals ensures minimal loss to follow-up. Nevertheless, the small sample size in the vaccinated group represents an important limitation, which makes it necessary to conduct further studies to confirm these findings.

The analysis of the consistency of the missing data showed a high percentage of missing data for the variables “Viral load” and “dTpa vaccination” among the characteristics of the pregnant women and for the variable “Cord arterial pH” among the characteristics of the neonate.

Conclusions

The findings analyzed in this study reinforce the effectiveness and safety of COVID-19 vaccination in pregnant women and the impact of SARS-CoV-2 infection in vaccinated versus unvaccinated pregnant women.This preventive measure is based not only on the reduction of symptoms with a single dose of the vaccine received by pregnant women who tested positive for COVID-19, but also on the fact that administering two or more doses reduces disease symptoms by up to 70%. Furthermore, it is not associated with an increase in obstetric complications or adverse effects in the newborn.

Likewise, the importance and need to continue with future research that expands the sample and allows for constant epidemiological monitoring to evaluate the long-term effects of vaccination during pregnancy, the impact of booster doses, as well as the effectiveness of vaccination against new SARS-CoV-2 variants in both the mother and the infant should be highlighted.

Public health strategies should promote access to vaccines during pregnancy as an urgent priority, to minimize the risk of serious complications from COVID-19. This is a community prevention measure supported by evidence of protection and benefit for the mother and fetus.