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

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.