New meta-analysis reaffirms ‘serious health risks’ from COVID-19 infection in pregnancy

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Against a backdrop of high neonatal and maternal relative risk, researchers of a new meta-analysis urge COVID vaccination for all women of childbearing age; ‘consistent and compelling’ evidence

A new meta-analysis involving more than 13,000 pregnant women has found “serious health risks” among those infected with the COVID-19 virus.(1) They had a seven times greater risk of death and a significantly increased risk of ICU admission or pneumonia than those who are not infected. In addition, the study also suggested that infection during pregnancy increases the risk of intensive care for the baby.

“The study provides the most comprehensive evidence to date suggesting that COVID-19 poses a threat during pregnancy,” the study’s lead author said in a press statement. “Our findings underline the importance of COVID-19 vaccination for all women of childbearing age.” While gathering the evidence has been difficult in the past, she adds, this meta-analysis now yields “clear, consistent, and compelling findings.”

Of course, this is not the first warning about the risks of COVID-19 during pregnancy, nor about neglecting the vaccine.(2) Data from many studies have shown that COVID infection during or before pregnancy increases the risk of death , ICU admission, preterm birth, stillbirth, preeclampsia and admission to neonatal care. But according to this latest report, these studies were often small, difficult to synthesize and heterogeneous in design. This latest meta-analysis, which pooled individual patient data from 12 eligible studies with 13,136 pregnant women, sought to avoid such anomalies. Nearly all of the COVID infections in the study were confirmed by PCR testing, with 11,194 women negative during pregnancy and 1942 positive.

The results of the comparison showed that COVID-19 during pregnancy increased the risk of maternal death, ICU admission, mechanical ventilation, possible intensive care unit, pneumonia or thromboembolic disease. In some of these the relative risks with no infection were very high: maternal mortality RR 7.68; ICU RR 3.81, ventilation RR 15.23; any intensive care unit RR 5.48; and pneumonia RR 23.46. Newborns of infected women were also more often admitted to intensive care, RR 1.86. However, unlike some findings from other studies, infection was not linked to stillbirth in this analysis.

The authors note that the results were intended to provide “robust and high-quality” estimates of the consequences of SARS-CoV-2 infection in pregnancy compared to uninfected pregnancies. And as such, they conclude that the findings “underscore the need for global efforts to prevent COVID-19 in pregnancy through targeted vaccine delivery and nonpharmaceutical interventions.” This goes one step further in a summary box appended to the research report describing access to preventive and therapeutic measures as ‘an urgent priority’.

Indeed, the authors’ press release – if not the published research report – calls on ‘all countries’ to prioritize COVID vaccines during pregnancy ‘to save lives and prevent health problems’. In support of her claim, the first author adds that, despite the serious health risks widely recognized, more than 80 countries still do not recommend that all pregnant and lactating women receive the COVID vaccine. This is evidenced by many still valid national guidelines that usually include vaccines in a range of mitigation strategies – and indeed, the joint IFFS/ESHRE statement on vaccines in pregnancy, albeit from 2021, concluded that “the decision to receive the vaccine whether to refuse depends on individual risk, vaccine availability, and potential recipients’ concerns about the unknown risks of the new vaccines’.(3) Recent studies have raised concerns that the vaccines could negatively affect ovarian function somewhat taken away, at least in an IVF model.(4)

Meanwhile, despite the 80 hesitant countries identified by the study’s authors, major health regulators all seem to recognize the risks posed by COVID infection during pregnancy; “getting a COVID-19 vaccine can help protect you and your baby from serious health problems,” the CDC advises; the UK Department of Health ‘strongly recommends’ vaccination during pregnancy; France ‘recommends’ a full panel of vaccines for pregnant women; and in Germany, in 2021, after much deliberation, authorities issued a recommendation for pregnant and breastfeeding women to get vaccinated. However, as the authors of the meta-analysis point out, many women of childbearing age still remain unvaccinated and this latest evidence “underscores the importance of COVID-19 vaccination for all women of childbearing age.”

1. Smith ER, Oakley E, Grandner GW, et al. Adverse maternal, fetal, and neonate outcomes in 1942 pregnant women with SARS-CoV-2 infection, compared with 11194 negative pregnancies: a meta-analysis of individual participant data. BMJ Global Health 2023; 8:e009495.
doi.org/10.1136/ bmjgh-2022-009495
2. See https://www.focusonreproduction.eu/article/News-in-Reproduction-COVID-vaccinations
3. Ory S, Veiga A, Horton A, Gianaroli L. Joint IFFS/ESHRE statement on COVID-19 vaccination for pregnant women and women considering pregnancy. Hum Reprod Open 2021, hoab016. https://doi.org/10.1093/hropen/hoab016
4. Dahdouh EM, Balayla J. SARS-CoV-2 Vaccines and IVF Results: So Good So Far! Fertil Sterile 2023;
doi.org/10.1016/j.fertnstert.2023.01.016

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