An Update on COVID-19 Vaccination and Pregnancy

Pregnant women are more prone to experience severe COVID-19 disease, including intensive care unit (ICU) admission, use of invasive ventilation, extracorporeal membrane oxygenation (ECMO), and mortality compared to non-pregnant individuals. Additionally, research suggests that SARS-CoV-2 infection during pregnancy is linked to adverse pregnancy outcomes, such as preterm birth, preeclampsia, and stillbirth, as well as adverse neonatal outcomes, including hospitalization and admission to the neonatal intensive care unit. This review assessed the available literature from November 2021 to 19 March 2023, concerning the safety and effectiveness of COVID-19 vaccination during pregnancy. COVID-19 vaccination administered during pregnancy is not linked to significant adverse events related to the vaccine or negative obstetric, fetal, or neonatal outcomes. Moreover, the vaccine has the same effectiveness in preventing severe COVID-19 disease in pregnant individuals as in the general population. Additionally, COVID-19 vaccination is the safest and most effective method for pregnant women to protect themselves and their newborns from severe COVID-19 disease, hospitalization, and ICU admission. Thus, vaccination should be recommended for pregnant patients. While the immunogenicity of vaccination in pregnancy appears to be similar to that in the general population, more research is needed to determine the optimal timing of vaccination during pregnancy for the benefit of the neonate.


Introduction
The effectiveness of COVID-19 vaccination was first reported in December 2020. Subsequently, mass vaccination of the general population took place [1]. Nonetheless, pregnant women were not included in initial COVID-19 vaccine trials due to concerns about the lack of prior experience with mRNA vaccines in this population and uncertainty about the potential risks to both the mother and fetus [1][2][3]. As a result, the available information on the long-term safety and efficacy of COVID-19 vaccines in pregnant individuals is currently limited to observational data [1,4]. This limited knowledge has contributed to vaccine hesitancy among pregnant women [1].
Regarding pregnancy outcomes, pregnant women with SARS-CoV-2 infection are at a heightened risk of preeclampsia/eclampsia, preterm birth, stillbirth, fetal distress, premature rupture of membranes, gestational diabetes, impaired fetal growth, and cesarean section, compared to pregnant women without the infection [7,[13][14][15][16][17][18][19][20][21]. about the type of COVID-19 vaccines used, number of doses administered, and timing of vaccination during pregnancy; and (4) results and conclusions of the studies. The basic characteristics of the included studies are summarized in Table 1.

Data Synthesis
A narrative review was conducted using the data gathered from the selected studies. ZOTERO was employed to sort out articles and remove any duplicates. The safety of COVID-19 vaccines during pregnancy was assessed by examining the potential adverse effects described in the literature.
The effectiveness of COVID-19 vaccines in pregnant women vaccinated during or before pregnancy was evaluated based on reported pregnancy outcomes. These included the incidence of SARS-CoV-2 infection, severe illness, hospitalization related to COVID-19, ICU admission, mortality, and other adverse maternal, fetal, or neonatal outcomes.
Ultimately, data reported in the literature concerning the benefits of maternal COVID-19 vaccination on the neonatal immune system was carefully reviewed.

Included Articles
When the initial literature research was conducted up to 19 March 2023, 177 articles were identified. After reviewing the titles and abstracts, 110 articles were excluded. Then, 33 more articles were excluded during the full-text review based on the inclusion and exclusion criteria. Screening the bibliography of the already selected ones, three additional articles were selected. As a result, 37 studies were included in the literature review. The literature retrieval flow diagram is presented in Figure 1.
pregnancy enhances the neonatal immune system against SARS-CoV-2 infection either through cord blood or breastfeeding transmission of antibodies.
The selected studies were analyzed for the following data: (1) basic information about the studies, such as publication year, first author, and study design; (2) characteristics of the study population, including the type of participants, sample size, and location; (3) details about the type of COVID-19 vaccines used, number of doses administered, and timing of vaccination during pregnancy; and (4) results and conclusions of the studies. The basic characteristics of the included studies are summarized in Table 1.

Data Synthesis
A narrative review was conducted using the data gathered from the selected studies. ZOTERO was employed to sort out articles and remove any duplicates. The safety of COVID-19 vaccines during pregnancy was assessed by examining the potential adverse effects described in the literature.
The effectiveness of COVID-19 vaccines in pregnant women vaccinated during or before pregnancy was evaluated based on reported pregnancy outcomes. These included the incidence of SARS-CoV-2 infection, severe illness, hospitalization related to COVID-19, ICU admission, mortality, and other adverse maternal, fetal, or neonatal outcomes.
Ultimately, data reported in the literature concerning the benefits of maternal COVID-19 vaccination on the neonatal immune system was carefully reviewed.

Included Articles
When the initial literature research was conducted up to 19 March 2023, 177 articles were identified. After reviewing the titles and abstracts, 110 articles were excluded. Then, 33 more articles were excluded during the full-text review based on the inclusion and exclusion criteria. Screening the bibliography of the already selected ones, three additional articles were selected. As a result, 37 studies were included in the literature review. The literature retrieval flow diagram is presented in Figure 1.

Safety of COVID-19 Vaccination during Pregnancy
Observational studies and large case series investigating COVID-19 vaccines in pregnancy have not found any significant adverse events related to the vaccines, apart from the ones commonly described for the general population, such as injection site pain, fever,
Ma Y et al. and Goldshtein et al. reported a 50% reduction in the risk of SARS-CoV-2 infection and COVID-19-related hospitalization with COVID-19 vaccination [10,45]. Other studies have also reported that vaccinated pregnant women have a lower frequency of infection before delivery compared to unvaccinated women [25,39,45]. Moreover, a study published by Kim et al. found that 4.1% and 25% of patients in the vaccination and nonvaccination groups, respectively, had severe symptoms, and 2.6% and 16.2% required oxygen therapy [46]. In this line, Ilter et al. reported in vaccinated pregnant people a significant reduction in the requirement for oxygen support (0.0 vs. 9.6%, p = 0.015) and the admission to an intensive care unit (0.0 vs. 3.8%) compared to the unvaccinated group [44]. Furthermore, in a recent study by Eid et al., a significant benefit was found in the vaccinated group with reduced COVID-19 severity, improved clinical results, and fewer hospital or ICU admissions [47].
Regarding obstetric outcomes, Stock et al. and Hui et al. have reported a decrease in stillbirth in pregnant individuals who received the COVID-19 vaccine [39,48]. In addition, a systematic review and meta-analysis found that COVID-19 vaccination was linked to a 15% reduction in stillbirth cases [1]. Watanabe et al. also provided evidence that the administration of COVID-19 vaccines in pregnancy reduced intrauterine fetal death [38].
Concerning preterm delivery, Hui et al. reported a significant decrease in total preterm births <37 weeks (5.1% vs. 9.2%), spontaneous preterm birth (2.4% vs. 4.0%), and iatrogenic preterm birth (2.7% vs. 5.2%) with COVID-19 vaccination [48]. In addition, Carbone et al. and Schrag et al. reported a reduced likelihood of lower gestational age at delivery, nonreassuring fetal monitoring, and a decreased rate of premature delivery in pregnant women who received the COVID-19 vaccine compared to those unvaccinated [43,49]. Table 1 summarizes the main maternal and neonatal benefits and risks of COVID-19 vaccination during pregnancy from the studies included in the review.

COVID-19 Vaccination and Potential Benefits for the Neonatal Immune System against SARS-CoV-2 Infection
Regarding hospitalization of newborns, a test-negative and case-control study conducted in 17 US states from July 2021 to January 2022 assessed the efficacy of mRNA vaccines during pregnancy against COVID-19-related hospitalization in infants under six months of age. The study revealed a vaccine effectiveness rate of 61%. Moreover, when administered within the first 20 weeks of gestation, two doses of the vaccine were 32% effective in preventing COVID-19-associated hospitalization in infants, whereas administering the vaccine from 21 weeks gestation through to 14 days before delivery resulted in an efficacy rate of 80% [17,25,40,43,53]. Another study found that maternal vaccination was 52% effective in preventing hospitalization for COVID-19 in infants. The effectiveness was higher at 69% when maternal vaccination was administered above 20 weeks of gestation and lower at 38% during the first 20 weeks of pregnancy [54]. Halasa et al. also pointed out that administering the SARS-CoV-2 vaccine during pregnancy could decrease the risk of infant hospitalization for COVID-19 by 30-70% up to 4-6 months of age [17]. In this line, Kugelam et al. recommend COVID-19 vaccination for pregnant individuals in the second trimester to provide protection for the mother and ensure the safety of the newborn [55]. Table 1. Main maternal and neonatal benefits and risks of COVID-19 vaccination in pregnancy from the studies included in the review.
Referring to adverse neonatal outcomes, various studies showed that the administration of the COVID-19 vaccine to pregnant individuals in the third trimester reduced the risk of neonatal adverse outcomes, including multisystem inflammatory syndrome in children (MIS-C) [3,52]. An extensive safety study conducted in Canada indicated that maternal vaccination might protect against low Apgar scores and admission to neonatal intensive care units [43]. Accordingly, Rottenstreich et al. reported that infants born to mothers vaccinated with two doses of mRNA vaccine during gestation had a 30% lower likelihood of COVID-19-associated admission to the ICU in the first six months of life [3]. Table 2 summarizes the results from the studies included in the analysis.  There was no significant link found between receiving a COVID-19 vaccine during pregnancy and a higher risk of adverse peripartum outcomes. There was no significant association between SARS-CoV-2 vaccination during pregnancy when compared to no SARS-CoV-2 vaccination during pregnancy and the risk of preterm birth, (aHR, 0.98), stillbirth (aHR, 0.86), SGA (aHR, 0.97), low Apgar score (aOR, 0.97), or neonatal care admission (aOR, 0.97).
Receiving the SARS-CoV-2 vaccine while pregnant did not raise the probability of negative pregnancy outcomes.
[24] Favre, G. Severe adverse events, such as venous thromboembolism, fever requiring hospitalization, and herpes zoster, were rare following COVID-19 vaccination. It was reported very low rate of early and late spontaneous abortion after COVID-19 vaccination during pregnancy, at 0.9% and 0.4%, respectively. There is no evidence suggesting that COVID- 19 vaccination during pregnancy increases the risk of preterm birth or SGA.
Pregnant individuals who were vaccinated did not encounter an elevated risk of negative outcomes during pregnancy or for their newborns. The administration of COVID-19 mRNA vaccination during pregnancy did not show a significant association with increased risk of adverse obstetric outcomes such as preterm birth, hypertensive diseases of pregnancy, cesarean delivery, and SGA. The vaccinated group had a significantly lower risk of meconium-stained amniotic fluid compared to the unvaccinated group.(aOR 0.63; 95% CI, 0.46-0.86, p = 0.0039). There was no significant association found between the COVID-19 vaccine and an increased risk of neonatal adverse outcomes, such as respiratory complications or neonatal intensive care unit (NICU) admission.
There was no significant correlation found between receiving the BNT162b2 messenger RNA vaccine during pregnancy and a higher incidence of negative obstetric or neonatal outcomes.
[26] Mascolo, A. There were no significant differences in the occurrence of harmful effects between pregnant women and non-pregnant women who received immunization. The examined pregnant women showed a robust humoral response after receiving BNT162b2 and Ad26.COV2.S vaccination.
Both the BNT162b2 and Ad26.COV2.S vaccines are secure to administer during the third trimester of pregnancy, with their effectiveness, safety, and immune response comparable to that of the general population. There is currently no evidence that mRNA vaccine products are present in maternal blood, placental tissue, or cord blood at delivery. The transfer of IgG and neutralizing antibodies from vaccinated pregnant women to their neonates is efficient and time-dependent, with the antibodies persisting during early infancy.
Administering mRNA vaccines during pregnancy is a secure practice and produces time-dependent functional, protective antibody responses in mothers and their infants, which remain effective during early infancy.

n = 34
Decidual biopsies obtained at delivery.
Eight women had COVID-19 in the first trimester, 17 women were fully vaccinated with 2 doses against COVID-19 during pregnancy, and 9 were neither infected nor vaccinated during pregnancy.
Pregnant women vaccinated with mRNA-1273 (Moderna) or BNT162b2 (Pfizer) at any time during pregnancy.
Lower levels of macrophages and natural killer cells (NK) were observed in the vaccinated cohort compared to the control group. There were no significant differences in cytokine levels between the vaccinated and control groups.
There was no correlation observed between vaccination and inflammation of the decidual tissue, indicating the safety of administering SARS-CoV-2 vaccines during pregnancy.   Administration of the COVID-19 vaccine during different periods of pregnancy can stimulate the production of antibodies, which may provide protection for both the mother and the child. The period between vaccination and birth was found to have an impact on the level of serum and breast milk antibodies.
Vaccination of the mother against SARS-CoV-2 has neonatal advantages due to the transfer of antibodies across the placenta during intrauterine development and through breast milk after delivery. The rate of COVID-19 vaccine coverage among pregnant women was significantly lower compared to the general female population of reproductive age. Unvaccinated pregnant women with COVID-19 had a higher incidence of severe complications, such as critical care admission and perinatal mortality, compared to pregnant women who had received the COVID-19 vaccine.
Vaccinating pregnant women against COVID-19 is crucial in preventing adverse outcomes related to the disease. Higher titers and functions against SARS-CoV-2 were found after the application of mRNA vaccines in pregnant women. Pregnant women who received COVID-19 vaccination in the first and third trimesters had enhanced maternal antibody-dependent NK-cell activation, cellular and neutrophil phagocytosis, and complement deposition compared to those who received vaccination in the second trimester. Compared to third-trimester vaccination, first and second-trimester vaccination resulted in higher transplacental transfer ratios.
This study shows that there is a higher concentration of functional antibodies in the umbilical cord and a greater transfer efficiency after receiving the first dose of the vaccine during the first trimester of pregnancy. Administration of a booster vaccine during the third trimester, as well as 6 months post-mRNA vaccines and two months post-Ad26.COV2.S vaccine may further enhance maternal and neonatal immunity for pregnant individuals who received their first dose during the first trimester. There were no major side effects reported during the COVID-19 vaccine administration, especially during the second and third trimester of pregnancy and during breastfeeding. Maternal vaccination against SARS-CoV-2 has been shown to result in a good maternal immune response, as well as the transfer of maternal antibodies through cord blood and breastfeeding, which can confer passive protection against the virus in newborns.
The benefits of getting vaccinated against COVID-19 during pregnancy for both mothers and infants are greater than the potential risks. Maternal vaccination has been shown to result in the transfer of maternal antibodies that provide passive protection against SARS-CoV-2 in newborns. Breast milk of vaccinated and infected mothers contains anti-SARS-CoV-2 antibodies, which may provide a protective effect on their newborns and infants. During the fourth surge of SARS-CoV-2, which was dominated by the Delta variant, pregnant patients who received SARS-CoV-2 vaccination had lower odds of experiencing severe or critical COVID-19, as well as any severity of COVID-19, compared to those who were unvaccinated. In vaccinated pregnancies, all cases of SARS-CoV-2 were either asymptomatic or mild, while in contrast, 9.6% of unvaccinated women experienced moderate or severe SARS-CoV-2 symptoms. Compared to the unvaccinated group, the vaccinated group exhibited a significant reduction in the requirement for oxygen support (0.0 vs. 9.6%, p = 0.015). In the unvaccinated group, the rate of admission to the intensive care unit was 3.8%, whereas no cases of admission were reported in the vaccinated group.
Fully vaccinated pregnant women who were infected with SARS-CoV-2 during the Omicron wave experienced milder illness and were less likely to require oxygen supplementation and intensive care compared to unvaccinated pregnant women. Vaccinated with at least 1 dose of any type of COVID-19 vaccine at any time during pregnancy.
There was a significant reduction in the rates of "moderate-to-severe" disease and the need for oxygen therapy in the vaccinated group as compared to the non-vaccinated group ( In the vaccinated group, none of the patients who later contracted COVID-19 progressed to severe or critical disease, whereas it was 7.2% in the unvaccinated group (p < 0.01). Individuals who received the vaccine and later developed COVID-19 were less likely to require hospital admission (1.6% vs. 14.7%, aOR 0.14, 95% CI = 0.22-0.47) compared with unvaccinated ones.
For pregnant individuals who receive a vaccination against SARS-CoV-2 and later experience a breakthrough infection, there is a lower probability of experiencing severe or critical COVID-19 and a reduced need for hospitalization or intensive care unit admissions. Compared to unvaccinated women, vaccinated women had a significantly lower rate of stillbirth (0.2% vs. 0.8%, 95% CI = 0.09-0.37, p < 0.001). There was a significant decrease in vaccinated individuals in the number of preterm births at less than 37 weeks (5.1% vs. 9.2%, 95% CI = 0.51-0.71, p < 0.001), spontaneous preterm birth (2.4% vs. 4.0%, 95% CI = 0.56-0.96, p = 0.02), and iatrogenic preterm birth (2.7% vs. 5.2%, 95% CI = 0.41-0.65, p < 0.001). Newborns delivered by vaccinated mothers exhibited lower rates of admission to NICU. Vaccinated women did not exhibit a significant increase in the rate of congenital anomalies or birth weight below the 3rd percentile. In comparison to the unvaccinated group, vaccinated women had a significantly lower likelihood of giving birth to an infant with a major congenital anomaly (2.4% vs. 3.0%, 95% CI = 0.56-0.94, p = 0.02).
Administering the COVID-19 vaccine during pregnancy resulted in a lower incidence of stillbirth and preterm birth and did not negatively affect the growth or development of the fetus. Although the probability of having a SGA fetus remained similar (OR 0.97, 95% CI 0.85-1.09, p = 0.570), vaccinated pregnant women showed a lower chance of experiencing non-reassuring fetal monitoring, a decrease in gestational age at delivery, and a lower likelihood of premature delivery compared to unvaccinated pregnant women.
There is a comparable probability of SGA between pregnant women who received the vaccine and those who did not, and vaccinated pregnant women also experienced a slightly lower incidence of premature delivery. Fully vaccinated mothers had an effectiveness rate of 61.6% (95% CI = 31.9-78.4), while there was no significant effectiveness observed for partially vaccinated mothers. The effectiveness was observed to be greater in infants aged 0-2 months compared to those aged 3-6 months. The OR for severe infection in infants born to fully vaccinated mothers was 5.8 times lower than that for infants born to unvaccinated mothers.
Infants under 6 months old whose mothers received at least two doses of the BNT162b2 vaccine during the second or third trimester of pregnancy experienced a 61.6% reduction in hospitalization rates for SARS-CoV-2 infection. [49] Halasa, N.B.
Pregnant women vaccinated with 2 doses of mRNA vaccine at any time during pregnancy.
The effectiveness of maternal vaccination in preventing hospitalization for COVID-19 among infants was 69% (95% CI = 50-80) when the vaccination was administered after 20 weeks of pregnancy. In contrast, the effectiveness was 38% (95% CI = 3-60) when the vaccination was given during the first 20 weeks of pregnancy.
Infants under 6 months of age whose mothers received a two-dose mRNA vaccine had a lower risk of hospitalization due to COVID-19, including critical illness. infections were predominantly observed in newborns whose mothers were not vaccinated and had non-severe COVID-19.  The evaluation of the risk of Multisystem Inflammatory Syndrome in Children (MIS-C) in infants born to vaccinated mothers has not been extensive. Vaccination of pregnant individuals results in the production of anti-spike protein IgG antibodies in maternal circulation, which are then passively transferred to the fetus through transplacental transport. These antibodies can be detected in newborns after birth and during early infancy and have a neutralizing effect against COVID-19 infection and its complications, including MIS-C.
Administering the COVID-19 vaccine to pregnant women led to a reduced risk of neonatal adverse outcomes, including MIS-C. [56] Martínez-Varea, A. Vaccinated with at least 1 dose of any type of COVID-19 vaccine at any time before or during pregnancy.
The probability of testing positive for cord-blood SARS-CoV-2 IgG antibodies was found to be 89% lower when the mother was infected with SARS-CoV-2 during the third trimester of pregnancy, in comparison to being infected during the first or second trimester.

Discussion
The present narrative review has evaluated the impact of SARS-CoV-2 vaccination on maternal, obstetric, and neonatal outcomes. The findings indicate that the uptake of the COVID-19 vaccine during pregnancy does not result in significant adverse events related to the vaccine or poorer outcomes for mothers, obstetric/fetal health, or neonates [1,3,7,10,12,18,24,[26][27][28][29][30]57]. In this line, data from the CDC v-safe registry, one of the largest international registries on COVID-19 vaccines during pregnancy, suggest that there are no apparent safety concerns related to COVID-19 vaccination in pregnancy in terms of obstetric or neonatal outcomes [58]. Additionally, the timing of COVID-19 vaccination during pregnancy does not have a significant impact on maternal-fetal outcomes [45]. The available evidence affirms that COVID-19 vaccination during pregnancy is safe and effective, regardless of the gestational age at which it is administered [58]. The main adverse effects of COVID-19 vaccination during pregnancy are the same as in the general population. Therefore, they usually appear within the first seven days, with local complications. Pain at the injection site is the most common one. Regarding systemic complications, fever would be the most frequent and potentially harmful to the fetus. Nonetheless, the use of antipyretics could help to reduce this risk [24,25,59,60]. It is important to note that the COVID-19 vaccine has not been specifically studied in pregnant women who have had complications associated with COVID-19. However, they may benefit from vaccination against COVID-19, as the vaccine can help to reduce the risk of severe illness and adverse outcomes [61].
Moreover, the vaccine's effectiveness appears to be comparable to that observed in non-pregnant individuals [1,5,27,39]. Studies examining vaccine effectiveness have reported varying rates ranging from 41% to 96%, depending on variables including the predominant COVID-19 variant at the time of the study, the vaccine dosage administered, and the outcome variable assessed (severe COVID-19, symptomatic COVID-19, or COVID-19 infection), among other variables [1,27,39]. In general, it is recommended that pregnant women follow the same dosage and administration interval recommendations for COVID-19 vaccination as those applied to the general population. Most COVID-19 vaccines approved so far require two doses, administered at a specific time interval depending on the vaccine type, to achieve maximum efficacy [58,62]. On the other hand, the FDA states that the results from SARS-CoV-2 antibody tests currently authorized should not be used to determine a person's level of immunity or protection against COVID-19 at any time, including gestation. These tests have not been validated to assess the level of protection, and if results are misinterpreted, there is a risk that individuals may take fewer precautions against SARS-CoV-2 exposure or may or may even choose not to get vaccinated when it is recommended [63].
Referring to neonates born from vaccinated mothers, studies show a lower rate of SARS-CoV-2 infection, hospitalization, ICU admission, and adverse neonatal outcomes such as MIS-C [3,5,15,17,25,40,43,[50][51][52][53]64,65,68]. This benefit to neonates is due to the fetal transfer across the placenta of anti-Spike IgG maternal antibodies induced by the vaccine, which offers stronger protection against SARS-CoV-2 infection during the first few months, with longer disease-free intervals correlated with higher antibodies levels at birth [69]. However, the protection afforded by infant antibodies against SARS-CoV-2 significantly diminishes after six months, highlighting the need for vaccination at this point to maximize defense against COVID-19 [69]. Since COVID-19 vaccines are not authorized for infants under six months, these findings support the notion that newborns benefit from maternal vaccination in terms of protection [25].
Noticeably, maternal vaccination induces a higher antibody response than natural infection, not only through cord blood antibody transmission but also in relation to the transfer of antibodies during breastfeeding [56,70,71]. In fact, breast milk from vaccinated mothers provides immediate protection through antibodies and long-term protection through cellular immunity [72]. Similarly, when referring to transplacental transfer, evidence suggests a direct association between the antibody levels found in maternal serum and cord blood, commonly defined as the placental transfer ratio [25,70,71]. The extent of maternal protection through the transfer of antibodies across the placenta relies on the concentration of antibodies in the maternal bloodstream, which is influenced by the moment of vaccination and delivery, suggesting that the interval between vaccination and birth may be a crucial factor in determining the degree of protection that the mother offers to her newborn [25,56].
Nonetheless, the ideal timing of COVID-19 vaccination in pregnancy to optimize neonatal benefit is still unclear [25,68]. Although the levels of maternal IgG and the transfer ratio of IgG across the placenta tend to rise as pregnancy progresses, the transfer of antibodies through the placenta usually begins during the second trimester, with the highest efficiency observed in the third trimester [25]. Administering the vaccine as soon as possible during gestation is essential to maximize the duration of maternal defense against infection. However, infant protection would depend on the efficiency and concentration of transplacentally acquired antibodies, which most studies suggest is higher during the third trimester [68]. Some studies have reported that all neonatal benefits are higher when mothers are vaccinated after 20 weeks of pregnancy [5,54]. Based on this hypothesis, some experts have recommended administering the booster vaccine in the early third trimester [25]. However, other studies support COVID-19 vaccination before conception or as early as possible during pregnancy to decrease the rate of severe COVID-19 disease during gestation and COVID-19 obstetric complications [40,73]. Nevertheless, at present, given that the majority of pregnant women are immunized against COVID-19, it should be noted that the absolute reduction in the risk after administering a booster dose in this population is likely to be small. Therefore, strategies for the complete vaccination of unvaccinated pregnant women would be more effective in reducing COVID-19 complications than offering booster doses to all those who are already immunized [74][75][76].
This study has several strengths, including its thorough search for evidence, rigorous selection criteria for the relevant literature, meticulous data collection, and objective analysis. Nonetheless, there are also some limitations to mention. Firstly, the retrospective nature of the study design introduces the potential probability of biases that are intrinsic to this type of study. Additionally, unknown factors could influence the findings, such as the impact of different COVID-19 variants and the gestational week at the moment of vaccination, both of which could affect maternal and neonatal outcomes. These factors should be further evaluated in future studies.

Conclusions
The safest and most effective method for pregnant women to safeguard themselves and their newborns from severe COVID-19 disease, hospitalization, and ICU admission is through COVID-19 vaccination. According to available data, there is no evidence of an increased risk of adverse outcomes for pregnant women, obstetric complications, or neonatal health problems following COVID-19 vaccination. Therefore, vaccination is recommended. The immunogenicity of vaccination in pregnant women appears to be comparable to that of the general population. However, the best timing for vaccination during pregnancy to benefit the newborn is still unclear, underscoring the need for further research.

Conflicts of Interest:
The authors declare no conflict of interest.