INTRODUCTION

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [1]. This novel beta coronavirus shares 79% genome sequence identity with SARS-CoV and 50% with Middle East respiratory syndrome coronavirus [2]. COVID-19 first emerged in Wuhan City, China, in December 2019 [3]. Shortly thereafter, the disease rapidly spread globally, with an estimated R₀ between 1.4 and 2.4, becoming a critical public health issue [4]. The World Health Organization declared the COVID-19 outbreak a public health emergency of international concern (PHEIC) on January 30, 2020, and characterized it as a pandemic on March 11, 2020 [5,6]. The PHEIC was lifted on May 5, 2023.

COVID-19 caused numerous infections and deaths worldwide. As of April 13, 2024, Worldometer data had recorded 704 753 890 cases and 7 100 681 deaths globally (worldometers.info/coronavirus). However, the actual burden may be much higher due to underreporting. Estimates indicate that only 1 in 4 COVID-19 cases and 1 in 3 COVID-19 deaths in the United States were reported [7].

To manage COVID-19, countries applied various strategies, which can be broadly categorized into containment and mitigation approaches [8]. Containment strategies focused on identifying and isolating infectious individuals and implementing social distancing measures. Mitigation strategies prioritized hospital care for severe cases rather than the early detection of all cases, isolated and treated mild cases, and screened and managed close contacts [9].

The first COVID-19 case in Vietnam was recorded on January 23, 2020 [10]. The country adopted a containment strategy (zero-COVID strategy), designed to reduce virus transmission to near-zero and eliminate the virus within specific geographic regions [11]. Key measures included border closures, isolating infected individuals, and wide-scale lockdowns following community transmission. Additionally, regular COVID-19 testing was conducted, and workplaces implemented on-site worker rotations. Later in the pandemic, Vietnam accelerated its vaccination campaign, shifting from zero-COVID to a strategy of safe adaptation, flexibility, and effective pandemic control [12]. Approximately 12 million COVID-19 cases and 43 206 deaths were recorded in Vietnam from the onset of the pandemic to June 19, 2023 [13].

During the strict COVID-19 prevention period, people were often required to remain at home except for essential activities. A wide range of services, including production, food supply, and healthcare, were impacted. Accordingly, anxiety regarding COVID-19 infection and the health status of relatives potentially exerted detrimental effects on health [14-16]. These factors could negatively affect pregnant female and fetal development, resulting in adverse birth outcomes [17]. Previous studies indicated that such birth outcomes were related to COVID-19 infection during pregnancy, including very preterm birth (PTB), early term birth, and low birth weight (LBW) [18,19].

However, research on the broader impacts of COVID-19 mitigation measures on birth outcomes remains limited. Thus, this study aimed to compare birth outcomes among mothers pregnant during and before the COVID-19 pandemic. We hypothesized that COVID-19 control measures negatively impacted infant health.

METHODS

Study Design and Setting

This retrospective cohort study utilized hospital records from 2016 to 2023 at Tu Du Hospital in Ho Chi Minh City (HCMC), Vietnam. HCMC, a southern province of Vietnam, is the country’s economic and commercial center. It is also the most populous city in Vietnam, with an estimated population of approximately 10 million as of 2023. HCMC covers an area of about 2095 square kilometers, divided into 21 districts and 1 city, with a population density of roughly 4000 people per square kilometer [20]. As one of HCMC’s 2 largest maternity hospitals, Tu Du Hospital specializes in obstetrics and serves a diverse urban population, making it an optimal setting for studying birth outcomes.

Data Collection

Data were extracted from electronic hospital records. Extracted variables included infant date of birth, sex, birth weight (BW), birth order, gestational age, and delivery method, as well as maternal age, weight, and residential address.

The inclusion criteria were infants born between 2016 and 2023 with an HCMC address. The exclusion criteria were infants with missing data on BW or sex, multiple gestations or stillbirths, BW <1500 g or >5500 g, and mothers aged <15 years or >59 years [21,22]. If any information for a study variable was missing, it was left blank.

Statistical Analysis

The dependent variables included BW, LBW, term LBW, and PTB. BW, defined as the weight of an infant at birth, is a continuous variable. LBW, term LBW, and PTB were treated as binary variables. LBW refers to a BW of less than 2500 g [22]. The BW and LBW analyses included infants with gestational ages from 32 weeks to 44 weeks [21]. Term LBW was defined as infants born between 37 weeks and 44 weeks of gestation and weighing less than 2500 g [22,23]. PTB referred to infants born alive before 37 weeks of gestation [17]. The study excluded cases with gestation periods under 20 weeks in the PTB analysis [22,23].

The study assessed differences in birth outcomes in HCMC between 2 distinct periods regarding the timing of pregnancy: before and during the COVID-19 pandemic. The COVID-19 pandemic was defined as occurring from April 2020 to December 2022, during which time the city implemented various control measures. Although the COVID-19 period could be subdivided into phases such as lockdown, partial reopening, or vaccination campaigns, this study considered the entire COVID-19 pandemic as a single phase.

For each infant, the estimated first day of pregnancy was calculated based on their date of birth and gestational age. Then, the durations of pregnancy within the pre-COVID-19 pandemic and pandemic periods were determined. The gestational phase during the COVID-19 pandemic was categorized as follows: (1) first trimester (weeks 1-13 of gestation occurring during the COVID-19 pandemic); (2) second trimester (weeks 14-26); (3) third trimester (week 27-birth); and (4) entire pregnancy (entire duration occurred during the COVID-19 pandemic) [21].

Statistical analyses were performed using R version 4.4.2 (R Foundation for Statistical Computing, Vienna, Austria). A t-test and logistic regression were employed to compare BW between the 2 periods. Odds ratios (ORs) and multivariable regression analyses were used to determine associations for binary outcomes (LBW, term LBW, and PTB) between the periods. Potential confounding variables related to the infant (sex, birth order, type of birth, gestational age) and mother (age and weight) were controlled by inclusion in the models. A p-value of less than 5% was considered to indicate statistical significance.

Ethics Statement

The Human Research Ethics Committee of the Institute of Public Health in HCMC, Vietnam, approved this study. All collected information remains confidential and is used solely for research purposes.

RESULTS

General Characteristics of Study Population

The study collected data on 175 286 infants born at Tu Du Hospital between 2016 and 2023. Among available records, 2328 (1.3%) were excluded due to missing or out-of-range BW data, 22 (0.01%) due to missing sex information, 917 (0.5%) due to maternal age under 18 years, and 2 due to gestational age being out of range. Overall, approximately 1.9% of records were excluded due to incomplete data on key variables.

Table 1 presents the general characteristics of the infants and their mothers. The average BW was 3177 g; female infants weighed approximately 72 g more than male babies. Among the infants, 52.0% were male, and 78.7% had a gestational age between 37 weeks and 40 weeks. Firstborn infants accounted for 44.2% of the total, and 50.4% were delivered via normal birth.

The proportions of LBW, term LBW, and PTB were 5.6%, 1.9%, and 8.6%, respectively. Female infants had a higher proportion of LBW and term LBW, whereas male infants predominated among instances of PTB.

The average maternal age was 30.7 years, with approximately 94% of mothers aged between 20 years and 39 years. The average maternal weight was 65.5 kg, and about 66.7% of mothers weighed between 55 kg and 70 kg. Approximately 31% of mothers experienced at least 1 trimester of pregnancy during the COVID-19 pandemic.

Supplemental Material 1 shows average BW by year of pregnancy. BW increased slightly from 2015 to 2018, followed by a decreasing pattern from 2019 to 2022.

Associations of Pregnancy During the Coronavirus Disease 2019 Period With Birth Outcomes

As shown in Table 2, mothers whose entire pregnancy occurred before the COVID-19 pandemic delivered babies weighing, on average, 20.7 g more than those pregnant during the COVID-19 pandemic—a statistically significant difference. In the subgroup analysis by infant sex, females exhibited a significantly greater decrease in BW than males (22.5 vs. 19.6 g; Supplemental Material 2). Comparable results were observed when analyzed by trimester. Infants whose first trimester occurred during COVID-19 experienced a slightly larger decrease in BW compared to the other trimesters (Table 2).

Mothers with the entire duration of their pregnancy during the COVID-19 pandemic displayed higher rates of LBW, term LBW, and PTB compared to those pregnant before the pandemic, with ORs (95% confidence intervals [CIs]) of 1.21 (1.15 to 1.27), 1.28 (1.18 to 1.39), and 1.10 (1.06 to 1.15), respectively (Table 3). Statistically significant differences were also observed when examining individual trimesters. In the sex analysis, male infants displayed a higher OR for term LBW, while female infants had a higher OR for PTB. The OR for LBW did not differ significantly by sex (Supplemental Material 3).

In the logistic regression model, which adjusted for potential confounders (infant sex, type of birth delivery, birth order, maternal age, and gestational age), pregnancy during the COVID-19 pandemic was associated with a statistically significant decrease of 14.5 g relative to the pre-COVID-19 period. No significant difference was observed between sexes (Supplemental Material 4).

Similar findings for LBW, term LBW, and PTB were confirmed by multivariable regression analysis, adjusting for infant sex, type of birth delivery, birth order, maternal age, and gestational age. The ORs (95% CIs) were 1.19 (1.12 to 1.26), 1.28 (1.18 to .1.39), and 1.10 (1.05 to 1.14), respectively (Supplemental Material 5).

DISCUSSION

This retrospective cohort study analyzed data from 172 017 infants born in HCMC between 2016 and 2023. Pregnancy occurring during the COVID-19 pandemic (April 2020 to December 2022) was associated with adverse birth outcomes relative to the pre-pandemic period, including lower BW and increased risks of LBW, term LBW, and PTB. Mothers who were pregnant during the COVID-19 pandemic delivered infants with an average BW 20.7 g lower than those pregnant entirely before the pandemic. Although this decrease in BW appears modest, it could reflect broader shifts in BW distribution, potentially increasing the proportion of infants at the lower end of the spectrum, including those classified as LBW. Such shifts could carry significant public health implications, as even small decreases in BW may elevate the number of infants needing additional neonatal care or facing long-term health challenges. Additionally, pregnancy during the COVID-19 pandemic was associated with a 21% (95% CI, 15 to 27) increased risk of LBW, a 28% (95% CI, 18 to 39) increased risk of term LBW, and a 10% (95% CI, 6 to 15) increased risk of PTB.

The negative associations of the COVID-19 pandemic with infant health may stem in part from the indirect effects of social distancing measures. Measures such as restrictions on gatherings, closures of schools and workplaces, work-from-home policies, and lockdowns effectively reduced SARS-CoV-2 transmission [24]. However, they likely contributed to boredom and isolation, adversely affecting psychological and mental health [14,16]. Lockdown measures also increased unemployment risk, low-income status, and family conflicts [15]. These socioeconomic stressors may have disproportionately impacted pregnant female, exacerbating mental health disorders and contributing to adverse birth outcomes [15]. Stress in pregnant female can activate the hypothalamus-pituitary-adrenal cortex axis, potentially increasing the risk of preterm birth [25].

During social distancing, pregnant female also faced food access limitations due to food insecurity [26], along with difficulties accessing healthcare services. Pregnant female may have reduced the frequency of obstetric care due to fears of COVID-19 infection or social distancing restrictions [27]. Additionally, medical staff shortages represented a potential contributing factor [28]. These disruptions likely increased risk for infants already at the lower end of the BW spectrum, elevating the incidence of LBW and the need for specialized neonatal interventions. The reported increase in home births and reduced antenatal care services during the initial COVID-19 pandemic period further compounded these risks [29].

Social distancing measures affected all aspects of physical activity and mental health. This study’s findings are consistent with a study of 198 203 infants in India, which reported an 8% increased risk of LBW for infants born during the COVID-19 pandemic compared to the pre-pandemic period, with BW 11 g lower [30]. A study from China found that pregnant female in the second trimester during lockdown had a 43% higher risk of PTB than those pregnant during the non-lockdown period. Additionally, third-trimester pregnancies during lockdown had a 64% higher risk of PTB accompanied by premature rupture of membranes compared to the non-lockdown period [17]. These consistent findings underscore the broad public health implications of the pandemic, including the potential for increased neonatal morbidity due to higher rates of LBW and PTB, thus necessitating enhanced monitoring and resource allocation for affected infants.

Adverse effects of the COVID-19 pandemic on infant health could result from maternal infection; however, this study could not analyze data on maternal COVID-19 infection status due to its unavailability. COVID-19 infection during pregnancy has been reported to increase the risk of PTB and reduced BW [31]. Among pregnancies occurring during the COVID-19 pandemic, the rate of LBW was 30.3%, compared to 18.7% in the non–COVID-19 pregnancy group [19]. In California, COVID-19 infection was associated with a 40% increased risk of PTB, a 10% increase in early preterm birth, and a 60% increase in very preterm birth [18].

However, the associations between the COVID-19 pandemic and birth outcomes have shown inconsistent results across studies, particularly concerning BW and LBW. Some studies have suggested increased BW during the COVID-19 pandemic, such as in Austria [32], Korea [33], and China [34], while a study conducted in Ireland [35], another study from China [17], and an investigation from Australia [36] did not report such differences. Other studies found insignificant associations between LBW rates and pregnancy during the COVID-19 pandemic versus before the pandemic [37,38]. Research in Kenya, Zambia, Congo, Pakistan, India, and Guatemala reported no impact of pregnancy during the COVID-19 pandemic on BW [29].

Potential explanations for these discrepancies include variations in COVID-19 control strategies across countries, such as quarantine measures and community responses, as well as regional differences in risk factors for adverse birth outcomes [39]. Another possible reason relates to differences in study design; for instance, a study in Austria compared birth outcomes of infants born during the COVID-19 pandemic versus before the pandemic, rather than comparing gestational periods within COVID-19 and non–COVID-19 contexts [32]. PTB rates have varied widely across studies, ranging from a 90% decrease to a 30% increase, following pandemic response measures. It remains unclear whether these variations are due to the impacts of lockdowns or to differences in stillbirth rates or study designs [40].

One strength of this study is that it provides evidence regarding associations between COVID-19 mitigation measures and adverse birth outcomes, including decreased BW and increased risks of LBW, term LBW, and PTB. Additionally, this study explored the relationship between the trimester(s) occurring during the COVID-19 period and adverse birth outcomes. However, this research has several limitations. First, the absence of data on maternal health conditions, such as gestational diabetes, hypertension, or anemia, limited the ability to control for medical confounders that could independently affect birth outcomes. Second, socioeconomic factors (such as education level, income, and occupation) and maternal COVID-19 infection status were not captured in hospital records. Consequently, the study could not account for their potential impacts on maternal stress, nutritional status, or access to antenatal care, all of which may mediate or modify the observed associations. Third, the study did not include data from all infants born in HCMC, potentially limiting the generalizability of the findings. Nonetheless, Tu Du Hospital is one of the two largest maternity hospitals in HCMC, suggesting that the results are likely representative of birth outcomes citywide. Additionally, we did not employ interrupted time series (ITS) regression, which might have better captured temporal trends in the association between COVID-19 exposure and birth outcomes. The staggered timing of conceptions posed challenges in defining a consistent intervention point for ITS analysis, leading to the use of linear and logistic regression models for the time-dependent predictor variable. Finally, as a retrospective observational study, this research could not definitively establish causality. Despite statistical adjustments, unmeasured or residual confounding remains possible.

In conclusion, pregnancy during the COVID-19 pandemic was associated with increased risks of LBW, term LBW, and PTB across all trimesters. Adequate prenatal care and social support should be emphasized for pregnant female during lockdowns or periods involving outbreak control measures.

Supplemental Materials

Notes

Conflict of Interest

The authors have no conflicts of interest associated with the material presented in this paper.

Funding

None.

Acknowledgements

The authors thank Tu Du Hospital for providing the infant databases and all colleagues at the Institute of Public Health for their assistance during data collection.

Author Contributions

Conceptualization: Ho Huu T, Tran Thi Thuy H. Data curation: Do Phuc Nhu N, Ho The N, Tran Thi Thuy H. Formal analysis: Ho Huu T, Ho The N. Funding acquisition: None. Methodology: Ho Huu T, Ho The N, Dang Van C. Project administration: Ho Huu T, Dang Van C. Visualization: Do Phuc Nhu N. Writing – original draft: Ho Huu T, Do Phuc Nhu N, Ho The N, Tran Thi Thuy H. Writing – review & editing: Ho Huu T, Dang Van C.

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