The data in this study were calculated based on the cohort data of 12,399,065 women of childbearing age (aged 15–49 years in 2019–2021) estimated by the Korean National Health Insurance Service. These data include information on the disease and prognosis of pregnant women and newborns based on COVID-19 and pregnancy. They also include reports on the vaccination status of women under the Korean National Health Insurance Service care (mostly Koreans), which started in 2021, as well as their obstetric prognosis after vaccination. The details include the following: (1) prognosis of women, diseases corresponding to codes O00–O94 defined by ICD-10, including cesarean section, which belongs to the category “Pregnancy, childbirth, and the puerperium,” and severe disease, which corresponds to the V code of the category “External cause of morbidity.” The prognoses of pregnant women with COVID-19 and those without infection have been previously described; (2) the prognosis of newborns, diseases corresponding to codes P00–P96, which belong to the category “certain conditions originating in the perinatal period” and neonatal intensive care unit (NICU) information. The prognosis of newborns born to pregnant women with COVID-19 and those born to pregnant women without COVID-19 are described; (3) number of vaccinations performed, description based on the type of vaccine, pregnancy, and age. For pregnant women who were vaccinated during pregnancy, the types of vaccine used, the number of gestational weeks at the time of vaccination, and obstetric outcomes based on the type of vaccine were analyzed.

First, non-pregnant (n=1,138,784) and pregnant (n=660,281) women were compared to determine whether COVID-19 has specific effects during pregnancy. Pregnant women were divided into two groups: pregnant women with and without COVID-19. They were compared to determine whether the two groups had different prognoses. In addition, the newborns of these women were compared to determine the effect of COVID-19 on their prognosis. Finally, pregnant women who were vaccinated during pregnancy were analyzed based on vaccine type, number of gestational weeks at the time of vaccination, and obstetric outcomes after vaccination.

We performed a chi-squared test to compare the distributions of the two groups. However, Fisher’s exact test was performed for cases in which more than 20% of cells had an expected frequency of <5, since applying the approximation method in these cases was considered inadequate (and the chi-squared test relies on approximation) [10].

Among the pregnant women, 0.11% were diagnosed with COVID-19 during pregnancy. Remarkably, the rate of various obstetric complications, including preterm birth and requirement for cesarean section, was significantly lower in pregnant women with COVID-19 than in those without COVID-19. Only the miscarriage (O02) rate increased in pregnant women with COVID-19 compared to those without COVID-19. Pregnant women with and without COVID-19 presented with approximately the same proportion of severe disease. COVID-19 also had no significant effect on fetal prognosis in almost all cases; however, newborns born to women with COVID-19 were significantly more vulnerable to birth injury to the scalp. In addition, newborns born to women with COVID-19 were more likely to be sent to the NICU. Vaccines were frequently administered within 28 weeks of pregnancy, and AstraZeneca and Janssen vaccines were associated with worse obstetric outcomes than mRNA vaccines, such as Pfizer and Moderna.

In this study, COVID-19 did not have a fatal effect on pregnant women and fetuses; however, COVID-19 was associated with an increased rate of miscarriage in early pregnancy. Remarkably, the results showed that pregnancy complications decreased in mothers diagnosed with COVID-19 during pregnancy. The lower complication rates and relatively good obstetric outcomes of COVID-19 during pregnancy indicate that acquiring this infection during pregnancy may not result in adverse outcomes, or that both pregnant women infected with COVID-19 and the medical staff were already aware of the potential implications of this infection. The most common SARS-CoV-2 variants in South Korea during the study period were B.1.1.7 (alpha) and B.1.620, which were different from other variants that were prevalent worldwide at that time (https://covariants.org/per-country). Different distributions of viral variants may be associated with good obstetric outcomes. Pregnant women with COVID-19 had a lower rate of preterm births and cesarean sections than those without COVID-19, and the rate of severe disease did not differ significantly between these groups. These results are not consistent with those of the United States Centers for Disease Control and Prevention COVID-19 surveillance system, in which pregnant women with COVID-19 were more likely to experience preterm birth or other adverse birth outcomes than those without COVID-19 [11,12]. Further studies are needed to clarify these conflicting results.

The phenomenon of lower preterm birth and cesarean section in pregnant women with COVID-19 require careful assessment. Several studies have reported a higher rate of preterm birth and cesarean section in pregnant women with COVID-19; however, some results are contradictory [13–20]. In addition, the most frequent causes of early emergency cesarean sections were reported to be fetal distress and worsening respiratory symptoms in pregnant women with COVID-19 [20]. There are several reasons that may contribute to the fact that pregnant women with COVID-19 had a low rate of preterm birth and cesarean section in our study compared to the results of several other studies.

First, this study used extensive and relatively updated data from November 2019 to July 2021. In a previous study, authors hypothesized that the rate of cesarean section decreased as experience in managing pregnant women with COVID-19 increased, since vaginal delivery does not appear to be associated with worse results in pregnant women or their newborns than cesarean section. Therefore, it seems appropriate that in our study, which included recent data, there was a lower rate of preterm birth and cesarean section associated with COVID-19.

Another reason that our results differ from those of some previous reports is that preterm birth or cesarean section may have been underreported among pregnant women with COVID-19, and it may be because many pregnant women with COVID-19 did not present to medical facilities out of fear. Strong support from medical facilities and staff is vital for pregnant women with COVID-19. Another explanation may be the changes in clinical practice due to the pandemic, which may have lowered the incidence of cesarean section or preterm birth among pregnant women with COVID-19 [21]. Although many complex factors must be considered regarding delivery timing and mode, infected women may have had reduced in-person appointments with obstetricians and, therefore, may not have undergone some interventions, such as labor induction.

Another explanation for the lower preterm birth rate in pregnant women with COVID-19 is modified behavior, such as wearing masks, washing hands, reduced physical exercise, reduced work-related stress, and earlier conservative treatment followed by quarantine, which results in a lower rate of infection from any source that may lead to preterm birth. This phenomenon was demonstrated in China and the UK before and after the pandemic, in which the preterm birth rate was lower after the pandemic [22,23].

Finally, another explanation is that pregnant women and fetuses receive special protection based on Korea’s COVID-19 response guidelines in circumstances where the infection itself does not seriously affect obstetric outcomes. South Korea used the “Three T Strategy,” which stands for testing, tracing, and treatment, enabling early detection and treatment of COVID-19 [24]. This strategy has ultimately led to low morbidity and mortality in the general population and maternity care regarding COVID-19, predominantly delta type, before December 2021, when the omicron type was not prevalent. During this period, pregnant women with COVID-19 or symptoms should notify infection specialists, obstetricians, and pediatricians before and during delivery, followed by quarantine to prevent the spread of infection to other people, and at the same time, doctors should immediately prepare appropriate plans based on the clinical conditions of pregnant women with COVID-19. Recently, in South Korea, the predominant type of COVID-19 has changed to omicron, which is a milder type with lower mortality, but spreads more easily. The fourth outbreak started in December 2021 and peaked in March 2022. The pandemic response strategy 3T against delta type has transformed into a new strategy because this milder omicron type causes more flu-like symptoms with lower fatality. To date, the fatality rate is approximately 0.13–0.15% and even lower in pregnant women. With the surge of COVID-19 in March 2022, the rate of infection has decreased and South Korea is about to reach the endemic stage.

The Korean government adopted a universal health coverage model during the COVID-19 pandemic in which all expenses related to COVID-19 are covered by the government, starting from 1st patient with COVID-19 in January 2020, which guided accessibility to medical care [25]. Due to the facilitated accessibility to health services, when pregnant women are diagnosed with COVID-19, they receive medical care before their symptoms worsen and the disease progresses. Indeed, in our study, there was no significant difference between the two groups regarding the proportion of severe diseases, unlike previous studies that described pregnant women with severe COVID-19 and adverse pregnancy outcomes, including intensive care unit admission [26]. In addition, in Korea, newborns born to pregnant women with COVID-19 or pregnant women presenting with COVID-19-related symptoms are quarantined in a negative-pressure bed in the NICU, regardless of whether intensive care is needed. Therefore, the NICU admission rate of newborns born to women with COVID-19 was significantly higher than that of newborns born to women without COVID-19. Therefore, with appropriate management, COVID-19 appears to have little effect on pregnant women and their fetuses. However, the rates of P3 (fetuses and newborns affected by other complications of labor and delivery) and P12 (birth injury to scalp) were significantly higher in fetuses of pregnant women with COVID-19 than in those of pregnant women without the infection. This prognosis is possibly due to the fact that more time is needed to prepare for delivery in pregnant women with COVID-19, and operative delivery is more likely to be adopted to shorten delivery time to avoid the spread of virus. Further studies are required to improve our understanding of these results. There is much evidence in the literature that vaginal delivery can be a risk factor for birth injury to the scalp, while cesarean delivery can be a protective factor [27,28]. Based on the data, we considered whether high birth injury to the scalp (P12 code) in neonates born to pregnant women with COVID-19 is related to the fact that this group had a low cesarean section rate, that is, a high vaginal delivery rate. The delivery mode appears to have a greater impact on perinatal outcomes than COVID-19 status.

Based on the results of the analysis of adverse reactions after vaccination released by the Korea Central Disease Control Headquarters, the rates of adverse reactions associated with the AstraZeneca and Janssen vaccines were 26.3% and 24.5%, respectively, which were higher than those of the Moderna and Pfizer vaccines (10.6% and 13.7%, respectively). The prognosis of pregnant women who received the AstraZeneca and Janssen vaccines was worse than that of pregnant women who received the Moderna and Pfizer vaccines because of the nature of the former two vaccines, which causes many abnormal symptoms, such as muscle ache, fever, fatigue, headache, Guillain Barre syndrome, and thrombocytopenia. In practice, mRNA vaccines such as Moderna and Pfizer have been reported to be safe for pregnant women and their fetuses [29]. A recent clinical study demonstrated no increased risk of preterm birth and no “small for gestational age” status after COVID-19 vaccination during pregnancy [30]. Therefore, at present, pregnant women are recommended to be vaccinated with mRNA products associated with fewer abnormal symptoms; however, further research is needed to clarify these results.

This study had several limitations. (1) All patients diagnosed with COVID-19 during the study period, in which infection did not occur during pregnancy, were excluded. Patients were also excluded if information regarding the timing of COVID-19 onset and pregnancy was unavailable. (2) Since this study was analyzed based on the National Health Insurance Claims database of South Korea, detailed medical information was not available from this database. For instance, if we had been able to examine the diagnostic codes, medications, and treatment data of 26 newborns who were hospitalized in the NICU after being born to mothers with COVID-19, it would have been clear whether these newborns needed intensive care. Due to data limitations, further analysis was difficult. Meanwhile, there was a higher rate of obstetric complications and a lower rate of spontaneous, operative, and other assisted single deliveries in our study population. Nevertheless, because the retrieved data were random, we did not choose certain preferable patients. (3) Owing to the known side effects of vaccines [31] and the country’s vaccination policy, the vaccination age range is not uniform for each vaccine. For example, the Janssen vaccine has only been administered to individuals over 30 years of age. It is already known that childbirth at an older age is highly risky and associated with a poor prognosis compared to childbirth at a younger age, and it includes risks such as preterm birth and Down syndrome. Therefore, age should be considered as an important factor in this study. However, we were provided with limited information regarding age; therefore, were not able to analyze age. (4) In this study, it was necessary to count each ICD-10 code, that is, 206 for O20 and 144 for O21 in the infected pregnant women group. However, several ICD-10 codes often correspond to the same disease. For example, to determine whether hypertension in pregnancy is applicable, we must also consider O10–16. However, we were provided with a count for each ICD-10 code, except for a few cases. Furthermore, because there may be overlapping targets between codes, we cannot arbitrarily combine them. And (5) in South Korea, all four types of vaccines were permitted between February and May 2021, and it has been recommended since October 8, 2021 that pregnant women should undergo vaccination. Considering the study period (November 2019 to July 2021), vaccination in most pregnant women is likely to have been voluntary without awareness of pregnancy status. The vaccinated subjects may have received only the first dose or both the first and second doses; however, in this study, these two cases could not be distinguished due to data limitations.

To the best of our knowledge, this is the first study to describe a detailed relationship between COVID-19 and obstetric outcomes in pregnant women and neonates based on the population data of Korean women. We found that the rates of preterm birth and cesarean section were significantly lower in women with COVID-19 than in women without infection. In addition, the rates of low birth weight, macrosomia, and NICU admission were comparable between infants born with and without maternal COVID-19 infection. However, since our study had several limitations, additional studies are needed to increase our understanding of the results. It is necessary to continuously monitor pregnant women and newborns who are vulnerable to COVID-19 through the establishment and periodic analysis of cohorts, including maternal factors related to the prognosis of pregnant women and newborns. We also found that an mRNA-based vaccine was less likely to be associated with adverse obstetric outcomes in pregnant women. The data we provide in this study may be useful in guiding the obstetric care of pregnant women during the COVID-19 pandemic.