Pregnant and recently pregnant women with coronavirus disease 2019 (COVID-19) are less likely to manifest COVID-19-related symptoms of fever and myalgia, but they may be at higher risk for admission to intensive care units (ICUs) and invasive ventilation compared with non-pregnant women of reproductive age, according to findings published in the British Medical Journal.
Results from the living systematic review and meta-analysis also indicate that mothers with pre-existing comorbidities appear to be at greater risk for severe COVID-19, along with those who are obese and of older maternal age. Further, preterm birth rates are higher in pregnant women with COVID-19, compared to those without the disease, and their neonates are more likely to be admitted to a neonatal unit.
Researchers led by John Allotey, Institute of Applied Health Research, University of Birmingham, Birmingham, UK, performed a literature search of major databases of relevant studies from December 1, 2019, to June 26, 2020, on COVID-19 in pregnant and recently pregnant women. “To minimise risk of bias we restricted our meta-analysis to cohort studies, and we reported the quality of the included studies. By contacting the authors and obtaining reports not published in PubMed, we minimised the risk of missing relevant studies. Our systematic review has a large sample size and it is continuously increasing. Our living meta-analyses framework will enable us to rapidly update the findings as new data emerge,” the authors said.
A total of 77 cohort studies, including 55 comparative and 22 non-comparative, were included in their systematic review. Overall, the studies included 13 118 pregnant and recently pregnant women with COVID-19, and 83 486 non-pregnant women of reproductive age with the disease. Forty cohort studies reported on clinical manifestations (13 018 pregnant, 85 084 non-pregnant women), 45 studies reported on COVID-19-related maternal outcomes (14 094 pregnant, 85 169 non-pregnant women), and 35 studies reported on pregnancy-related maternal (6279 women) and perinatal outcomes (2557 neonates).
The overall rate of COVID-19 diagnosis in pregnant women attending or admitted to hospital for any reason was 10% (95% confidence interval 7% to 14%; 26 studies, 11 432 women), with rates varying according to whether women were sampled by universal screening (7%) or on the basis of symptoms (18%). All studies with a prevalence rate of over 15% were from the US, except for one study, which was from France.
The most common clinical manifestations of COVID-19 in pregnancy were fever (40%) and cough (39%), while lymphopaenia (35%) and raised C-reactive protein levels (49%) were the most common laboratory findings. When compared with non-pregnant women of reproductive age with COVID-19, pregnant women with the disease were less likely to report fever (odds ratio [OR] 0.43, 95% CI 0.22 to 0.85; 5 studies, 80 521 women) and myalgia (OR 0.48, CI 0.45 to 0.51; 3 studies, 80 409 women). However, the odds of admission to the ICU (OR 1.62, CI 1.33 to 1.96) and need for invasive ventilation (OR 1.88, CI 1.36 to 2.60) were higher in pregnant and recently pregnant women (4 studies, 91 606 women).
Overall, 73 pregnant women (26 studies, 11 580 women) with confirmed COVID-19 died from any cause (0.1%, CI 0.0% to 0.7%), while severe COVID-19 disease was diagnosed in 13% (CI 6% to 21%; 21 studies, 2271 women) of cases. Increased maternal age (OR 1.78, CI 1.25 to 2.55; 4 studies; 1058 women), high body mass index (OR 2.38, CI 1.67 to 3.39; 3 studies; 877 women), chronic hypertension (OR 2.0, CI 1.14 to 3.48; 2 studies; 858 women), and pre-existing diabetes (OR 2.51, CI 1.31 to 4.80; 2 studies; 858 women) were associated with severe COVID-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for ICU admission (OR 4.21, CI 1.06 to 16.72; 2 studies; 320 women) as well as invasive ventilation (OR 4.48, CI 1.40 to 14.37; 2 studies; 313 women).
The overall rate of preterm births in COVID-19 pregnant women was 17% (CI 13% to 21%; 30 studies, 1872 women), while spontaneous preterm births occurred at a rate of 6% (3% to 9%; 10 studies, 870 women). The likelihood of any preterm birth (OR 3.01, CI 1.16 to 7.85; 2 studies; 339 women) was higher in pregnant women with COVID-19 compared to those without, but the authors noted there were no differences seen in other maternal outcomes.
In addition, 25% (CI 14% to 37%; 17 studies, 1348 women) of neonates born to women with COVID-19 were admitted to the neonatal unit, with a higher risk of admission (OR 3.13, CI 2.05 to 4.78; 1 study, 1121 neonates) than those born to mothers without the disease in one study with historical controls. No differences were observed for other perinatal outcomes.
“Further data are needed to assess robustly if pregnancy-related maternal and neonatal complications are increased in women with COVID-19 than those without the disease. Similarly, the association between other risk factors such as ethnicity and pregnancy-specific risk factors such as pre-eclampsia and gestational diabetes on both COVID-19-related and pregnancy-related outcomes needs evaluation,” the authors said.
“In this unprecedented pandemic situation, where evidence is rapidly produced and published in various formats, our living systematic review [is] underpinned by robust methods and continually updated at regular intervals,” the authors said, adding that their work “will produce a strong evidence base for living guidelines on COVID-19 and pregnancy.”