Impact of COVID-19 on Fetal Outcomes in Pregnant Women: A Systematic Review and Meta-Analysis

Abstract

Background: Coronavirus disease (COVID-19) is a pandemic causing respiratory symptoms, taste alterations, olfactory disturbances, and cutaneous, cardiovascular, and neurological manifestations. Recently, research interest has shifted to reproductive health to understand the factors predisposing to COVID-19 infection in pregnancy, the consequences of the infection on the fetus and on the mother, and possible vertical transmission through the placenta. Pregnancy does not increase the risk of SARS-CoV-2 infection, according to studies. However, contrary to non-pregnant women, pregnancy worsens the clinical outcome of COVID-19. Studies investigating the effects of COVID-19 on pregnancy women are heterogeneous, and the results are often conflicting. Objectives: The goal of the current work was to offer a thorough and up-to-date systematic review of, and meta-analysis on, the impact of COVID-19 on ovarian function, pregnancy, and fetal outcomes. Search strategy: This meta-analysis (PROSPERO n. CRD42023456904) was conducted using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. The search for relevant material was conducted using PubMed, Scopus, Cochrane, and Embase databases, through to 15 December 2022. Selection criteria: Original articles on fertile pregnant women or women attempting to become pregnant, with an active case of, or history of, SARS-CoV-2 infection were included, and reproductive function was compared to that of uninfected women. Data collection and analysis: The effects of COVID-19 on female reproductive function, particularly ovarian function, the profile of female sex hormones, pregnancy outcomes and fetal outcomes were the focus of our search. Quantitative analysis was performed with Comprehensive Meta-Analysis Software. The standard difference of the mean was calculated for the statistical comparison between cases and controls. Cochran's Q test and heterogeneity (I²) indexes were used to assess statistical heterogeneity. Sensitivity analysis and publication bias tests were also performed. Main Results: Twenty-eight articles met our inclusion criteria, for a total of 27,383 patients pregnant or looking to have offspring, with active or anamnestic COVID-19, and 1,583,772 uninfected control women. Our study revealed that there was no significant difference between COVID-19 patients and the control group in terms of maternal characteristics such as age, body mass index (BMI) and comorbidities that could affect pregnancy and fetal outcomes. The risk of a miscarriage or Cesarean delivery was significantly lower, while the risk of fetal death or premature delivery was significantly higher in COVID-19 patients than in the controls. None of the included studies evaluated hormonal profiles or investigated the presence of infertility. Conclusions: Maternal comorbidities, age, and BMI do not raise the risk of COVID-19. However, pregnant women with COVID-19 had a lower risk of miscarriage and Cesarean delivery, possibly because of better prenatal care and high levels of observation during labor. COVID-19 during pregnancy increases the risk of fetal death and premature delivery.

Keywords: COVID-19; SGA; birthweight; delivery; fetal death; miscarriage; pregnancy.

Figure 1

PRISMA flow diagram of the literature screening.

Figure 2

Forest plot of the risk for miscarriage in patients and controls. Crovetto et al., 2021 [19]; Wang et al., 2021 [8]; Bortoletto et al., 2021 [27]; la Cour Freiesleben et al., 2021 [37].

Figure 3

Forest plot of the risk for chorioamnionitis in patients and controls. Glynn et al., 2021 [15]; Brien et al., 2021 [20]; Bertero et al., 2021 [22]; Blasco Santana et al., 2021 [29]; Rebutini et al., 2021 [30]; Resta et al., 2021 [31]; Jaiswal et al., 2021 [32]; Patberg et al., 2021 [33].

Figure 4

Forest plot of difference in birth weight in patients and controls. Glynn et al., 2022 [15]; Laresgoiti-Servitje et al., 2021 [23]; Tasca et al., 2021 [26]; Abedzadeh-Kalahroudi et al., 2021 [44]; Jaiswal et al., 2021 [32]; Patberg et al., 2021 [33]; Tadas et al., 2021 [36]; Taglauer et al., 2020 [40].

Figure 5

Forest plot of difference in pre-term delivery in patients and controls. Lankford et al., 2021 [16]; Brien et al., [20]; Gurol-Urganci et al., 2021 [21]; Laresgoiti-Servitje et al., 2021 [23]; Tasca et al., 2021 [26]; Levitan et al., 2021 [28]; Abedzadeh-Kalahroudi et al., 2021 [44]; Rebutini et al., 2021 [30]; Verma et al., 2021 [46]; Cribiù et al., 2021 [34]; Smithgall et al., 2020 [38]; Donati et al., 2020 [41].

Figure 6

Forest plot of the risk for Cesarean delivery in patients and controls. Glynn et al., 2022 [15]; Crovetto et al., 2021 [19]; Brien et al., [20]; Gurol-Urganci et al., 2021 [21]; Laresgoiti-Servitje et al., 2021 [23]; Januszewski et al., 2021 [24]; Maeda et al., 2021 [25]; Tasca et al., 2021 [26]; Jang et al., 2021 [47]; Verma et al., 2021 [46]; Resta et al., 2021 [31]; Jaiswal et al., 2021 [32]; Patberg et al., 2021 [33]; Cribiù et al., 2021 [34]; Tadas et al., 2021 [36]; Smithgall et al., 2020 [38]; Donati et al., 2020 [41].

Figure 7

Forest plot of difference in gestational age at delivery in patients and controls. Ruggiero et al., 2021 [17]; Crovetto et al., 2021 [19]; Abedzadeh-Kalahroudi et al., 2021 [44]; Resta et al., 2021 [31]; Patberg et al., 2021 [33]; Tadas et al., 2021 [36]; Taglauer et al., 2020 [40].

Figure 8

Forest plot of the risk for small for gestational age in patients and controls. Glynn et al., 2022 [15]; Crovetto et al., 2021 [19]; Gurol-Urganci et al., 2021 [21]; Abedzadeh-Kalahroudi et al., 2021 [44]; Patberg et al., 2021 [33]; Debelenko et al., 2021 [35]; Gulersen et al., 2020 [39].

Figure 9

Forest plot of the risk for fetal death in patients and controls. Forest plot of the risk for small for fetal death in patients and controls. Lankford et al., 2021 [16]; DeSisto et al., 2021 [18]; Crovetto et al., 2021 [19]; Gurol-Urganci et al., 2021 [21]; Laresgoiti-Servitje et al., 2021 [23]; Jaiswal et al., 2021 [32]; Debelenko et al., 2021 [35]; Tadas et al., 2021 [36].