Association of Infection with Different SARS-CoV-2 Variants during Pregnancy with Maternal and Perinatal Outcomes: A Systematic Review and Meta-Analysis

Abstract

The aim of this study is to review the currently available data, and to explore the association of infection with different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants during pregnancy with maternal and perinatal outcomes in the real world. Observational cohort studies were analyzed that described the maternal and perinatal outcomes of infection with different SARS-CoV-2 variants during pregnancy. Random-effects inverse-variance models were used to evaluate the pooled prevalence (PP) and its 95% confidence interval (CI) for maternal and perinatal outcomes. Random effects were used to estimate the pooled odds ratios (OR) and their 95% CI for different outcomes between Delta and pre-Delta periods, and between Omicron and Delta periods. Eighteen studies, involving a total of 133,058 cases of SARS-CoV-2 infection during pregnancy (99,567 cases of SARS-CoV-2 wild type or pre-variant infection and 33,494 cases of SARS-CoV-2 variant infections), were included in this meta-analysis. Among pregnant women with SARS-CoV-2 infections, the PPs for required respiratory support, severe or critical illness, intensive care unit (ICU) admission, maternal death, and preterm birth <37 weeks were, respectively, 27.24% (95%CI, 20.51–33.97%), 24.96% (95%CI, 15.96–33.96%), 11.31% (95%CI, 4.00–18.61%), 4.20% (95%CI, 1.43–6.97%), and 33.85% (95%CI, 21.54–46.17%) in the Delta period, which were higher than those in the pre-Delta period, while the corresponding PPs were, respectively, 10.74% (95%CI, 6.05–15.46%), 11.99% (95%CI, 6.23–17.74%), 4.17% (95%CI, 1.53–6.80%), 0.63% (95%CI, 0.05–1.20%), and 18.58% (95%CI, 9.52–27.65%). The PPs for required respiratory support, severe or critical illness, and ICU admission were, respectively, 2.63% (95%CI, 0.98–4.28%), 1.11% (95%CI, 0.29–1.94%), and 1.83% (95%CI, 0.85–2.81%) in the Omicron period, which were lower than those in the pre-Delta and Delta periods. These results suggest that Omicron infections are associated with less severe maternal and neonatal adverse outcomes, though maternal ICU admission, the need for respiratory support, and preterm birth did also occur with Omicron infections. Since Omicron is currently the predominant strain globally, and has the highest rates of transmission, it is still important to remain vigilant in protecting the vulnerable populations of mothers and infants. In particular, obstetricians and gynecologists should not ignore the adverse risks of maternal ICU admission, respiratory support, and preterm births in pregnant patients with SARS-CoV-2 infections, in order to protect the health of mothers and infants.

Low Interferon-γ Levels in Cord and Peripheral Blood of Pregnant Women Infected with SARS-CoV-2

“…Regarding neonatal outcomes, regarding neonatal length, birthweight, head circumference and Apgar score, we observed no significant differences between cases and controls. These findings are consistent with the literature, particularly in reference to the alpha variant of SARS-CoV-2 [ 42 , 43 , 44 ]. There are differences in the response of the immune system (in the mother and fetus) and symptoms among SARS-CoV-2 variants [ 45 , 46 ].…”

Serological responses to the BNT-162b2 Pfizer/BioNTech vaccination in twin pregnancies- Comparison between immunization before conception and during pregnancy.

“…Extensive studies support the importance of vaccination of gravid subjects before and during pregnancy and have con rmed its e cacy in reducing the rate of infection and protecting them from severe symptoms [20]. However, no studies have explored twin pregnancies [21]. The current study provides the rst detailed evidence on the natural history of neutralizing Anti-S-IgG in twin pregnancies.…”

Maternal and Perinatal Outcomes of SARS-CoV-2 and Variants in Pregnancy

“…A recent meta-analysis of 18 studies revealed that pregnant women infected with the Delta variant were more likely to suffer preterm birth at less than 37 weeks of gestation than the pre-Delta group ( OR , 3.45; 95% CI , 1.17–10.15), whereas those with Omicron infection had a lower risk ( OR , 0.21; 95% CI , 0.11–0.40). Differences in other perinatal outcomes, such as stillbirth, were not significant when compared between the pre-Delta, Delta, and Omicron groups 98 . Even in full-term newborns during the Omicron period, neonates born to infected mothers had an increased risk of lower birth weight, lower Apgar scores, and an increased risk for respiratory support until 12 hours after birth when compared with those born to mothers without infection 99 .…”

“…Differences in other perinatal outcomes, such as stillbirth, were not significant when compared between the pre-Delta, Delta, and Omicron groups. 98 Even in full-term newborns during the Omicron period, neonates born to infected mothers had an increased risk of lower birth weight, lower Apgar scores, and an increased risk for respiratory support until 12 hours after birth when compared with those born to mothers without infection. 99 Boly et al 100 described three premature newborns from women with confirmed Delta infection with very low birth weight (<1500 g) and reported that all three infants presented with hyperglycemia and bone marrow dysfunction.…”

“…109,110 However, there was no difference in early neonatal infection within four weeks of maternal diagnosis when compared between the pre-Delta, Delta, and Omicron epochs, as reported by Adhikari et al 58 Similar findings were also demonstrated by a recent meta-analysis featuring 99,567 cases of SARS-CoV-2 wild-type or prevariant infections and 33,494 cases of SARS-CoV-2 variant infections, thus suggesting a comparable prevalence of neonatal SARS-CoV-2 positivity between the pre-Delta, Delta, and Omicron groups. 98 Because the risk of vertical transmission for SARS-CoV-2 is rare, comparative information based on different variants is limited; thus, further research is needed to fully understand the mechanisms by which maternal COVID-19 infection affects fetuses and newborns with the emergence of more new variants.…”