The year 2020 saw the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which became a great threat to public health worldwide. The epicenter of the outbreak was reported in Wuhan City, China in December 2019 (1). Subsequently, it spread like wildfire to the rest of the world and became a nightmare scenario as the number of deaths in conjunction to this infection increased drastically. Unfortunately, the effective treatment and definitive cure is yet to be discovered. The exponential spread of the disease with millions of lives lost worldwide saw the emergence of an accelerated vaccine development with emergency approval from well-known regulatory bodies such as the US Food and Drug Administration, followed by widespread vaccine deployment despite a paucity in safety profile data. Amongst pregnant women, data was even scarcer as they were not represented in the original clinical trials, especially when the expectant women have to consider the possible undesirable effect toward the unborn child as well.

Literature has revealed that pregnant women with severe COVID-19 infection are at increased risk for preterm birth and even pregnancy loss (2). As a whole, when compared to non-pregnant women, those who are pregnant are at higher risk of acquiring multiple complications through COVID-19 infection which may consequently result in greater mortality rate (3). Therefore, it is crucial to prevent COVID-19 infection from spreading through mass vaccination to attain herd immunity. In fact, medical bodies all around the world including the WHO, the Centers for Disease Control and Prevention (CDC), and Advisory Committee on Immunization Practices (ACIP), in collaboration with the American College of Obstetricians and Gynecologists and the American Academy of Pediatrics, have issued guidance recommending vaccines for pregnant women, especially those at highest risk (4–6).

Multiple studies have reported on the potential benefits of mRNA vaccines over live attenuated virus vaccines, inactivated or subunit vaccines, and DNA-based vaccines (7). In fact, they are manufactured by many registered pharmaceutical companies such as Astra Zeneca, Pfizer, etc. and are distributed worldwide in conjunction with the mass vaccination program. In Malaysia, there are two types of vaccines available, namely Pfizer/BioNTech (BNT162b2) and Oxford/AstraZeneca (AZD1222). However, only Pfizer is approved to be used in pregnant women by the National Pharmaceutical Regulatory Agency (NPRA), Malaysia, which is the mRNA COVID-19 (8). The safety profile for mRNA COVID-19 vaccine is yet to be established (9).

Therefore, it is necessary to establish the safety data in real time through rigorous proactive data collection to record both vaccine-related symptoms as well as obstetric outcomes which will advance current understanding on the symptoms encountered. Additionally, it provides further guidance for pregnant people to get vaccinated and also for the national policy holders during policy formulation.

This study was initiated once the Ministry of Health, Malaysia encouraged pregnant health care workers to be vaccinated and this study included the very first batch of volunteers to be vaccinated from March 2021 onwards. These subjects who consented to participate in this study were followed until their respective delivery dates. The sample size was undeniably small, but it represented 15% of the total Malaysian population. Additionally, no similar study was conducted elsewhere in Asia and so this study would provide the baseline data among this population group. Under the national procurement policy, only Pfizer was used with multiple batches of vaccines. A total of 121 pregnant healthcare employees participated in this study with the highest percentage of 57% (n = 69) from the 30–39 years of age category and up to 71.9% (n = 87) from the second trimester when the subjects received the first dose of the mRNA COVID-19 vaccine. Although the recommended dosing interval between the first and second dose was 3 weeks, the median (IQR) interval in this study was found to be 21 weeks as the Ministry of Health did not impose any restrictions on the permitted dosing gap between two doses. The majority of them, 91% (n = 109), received the mRNA COVID-19 vaccine within the recommended dosing interval. However, only four out of 121 subjects tested positive for COVID-19 infection post-mRNA vaccination despite all four individuals being vaccinated within the recommended dosing interval and having no comorbidities. All of them were hospitalized and were categorized as non-severe COVID-19 (12). All of them had a full recovery without any complications. The overall demographics and post-vaccination characteristics after mRNA COVID-19 vaccination by pregnant healthcare employees in general hospitals in Penang is depicted in Table 1. All the lab investigations pertaining to the blood parameters taken during subjects' antenatal visits were reported to be normal.

The majority of the study participants, ~74.2% (n = 92), had no previously reported significant antenatal history (ANC) history and another 60.6% (n = 77) had no actively reported ANC history for current pregnancies. Additionally, a majority of them, 91.1% (n = 113), had no reported known allergies to medications. It is further tabulated in Table 2.

The study population in this study consists of participants who received mRNA COVID-19 vaccine in all the trimesters of pregnancy. The total documented adverse effects associated to the mRNA COVID-19 vaccine in Penang which was reported to the National Pharmaceutical Regulatory Agency (NPRA) till December 2021 were 142 reports. Out of the total number, only four reports were associated with pregnant individuals who were enrolled in this study. The first reported adverse effect post mRNA COVID-19 vaccine was severe nausea and vomiting (21 weeks pregnant at the time of complaint) which required admission for close monitoring. Symptoms resolved gradually within 2 days after the administration of Veloxin Tablet. The second report was related to chest tightness accompanied with shortness of breath (29 weeks pregnant at the time of complaint) which also required hospitalized for close monitoring. No specific treatment was initiated as electrocardiogram (ECG) showed sinus rhythm and symptoms resolved spontaneously thereafter. The third reported adverse effect was generalized body rashes involving maculo-papular rash (exanthem) over all limbs and upper trunk of the body (27 weeks pregnant at the time of complaint). Symptoms were controlled with regular application of aqueous and steroid-containing cream. This participant required only one dose of Hydrocortisone intravenously. The fourth report was quite devastating, involving severe vaginal bleeding which consequently led to miscarriage (22 weeks pregnant at the time of complaint). This participant did not receive the mRNA COVID-19 vaccine during the first trimester. A definite conclusion failed to be made that this miscarriage was attributed to the mRNA COVID-19 vaccine. In comparison of the risk of miscarriage post mRNA COVID-19 vaccine, it was found to be ~0.8% in this study vs. up to 2.6% in the other study (9).

Looking into the neonatal outcomes, the studied parameters were small for gestational age, presence of congenital anomalies, preterm birth (<37 week), and also neonatal death. For all the parameters, the calculated incidences were almost similar to the published incidences in the other peer reviewed literature which was conducted prior to the COVID-19 pandemic except small for gestational age (17–24). The incidence of small for gestational age in this study seems to be higher, at 5.8% compared to the incidences published in other studies mentioned above.

However, the top five commonly reported symptoms post mRNA COVID-19 vaccine among the pregnant women were similar to what was reported via V-safe Pregnancy Registry (9).

There are two limitations encountered in this study. Firstly, the sample size is comparatively small as certain congenital anomalies are considered rare. Therefore, occurrence of such rare disorders requires large-scale recruitment. Secondly, the neonates are monitored up to 28 days only. The adverse effects presented beyond this period remain undocumented, especially certain chronic conditions which could possibly be noticed or known in the later stage of their lives.

As a whole, the inference that can be made from this study is mRNA COVID-19 vaccine appears to be safe in pregnant women regardless of the trimester as the findings did not show obvious safety warning signs. Nevertheless, recruiting larger numbers of participants and preferably with longitudinal monitoring is crucial to further strengthen the conclusion made earlier.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

The studies involving human participants were reviewed and approved by Medical Research and Ethics Committee (MREC) Malaysia. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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