By Richard R. Watkins, MD, MS, FACP, FIDSA, FISAC
Professor of Internal Medicine, Northeast Ohio Medical University, Rootstown, OH
SYNOPSIS: A meta-analysis and systematic review that included 24 studies mostly from China found that the rates of preterm birth and cesarean delivery were higher in women with COVID-19 compared to international averages.
SOURCE: Matar R, Alrahmani L, Monzer N, et al. Clinical presentation and outcomes of pregnant women with coronavirus disease 2019: A systematic review and meta-analysis. Clin Infect Dis 2021;72:521-533.
The management of a pregnant woman with COVID-19 represents a unique situation in clinical practice because there are two patients: the mother and her baby. Understanding the clinical course of COVID-19 during pregnancy is important so that a standard of care that leads to optimal outcomes for both mother and child can be developed. Matar and colleagues conducted a systematic review and meta-analysis of pregnant women with COVID-19 with this goal in mind.
The inclusion criteria for the study were: pregnant women; COVID-19 infection confirmed by reverse-transcription polymerase chain reaction (RT-PCR) from throat and/or nasal swabs; and available neonatal outcome data. Twenty-four studies were included in the systematic review and meta-analysis with a total of 136 pregnant women. The maternal age ranged from 25 to 34 years, and the gestational age at the time of admission ranged from 30 to 40 weeks. Of the 24 studies, eight were randomized controlled trials, 14 were case reports or case series, one was a prospective cohort study, and one was a case-control study. All of the patients were hospitalized during the course of delivery and treatment.
The most common presenting symptom was fever, which occurred in 62.9% of patients (95% confidence interval [CI], 0.477-0.759). Cough occurred in 36.8% (95% CI, 0.253-0.500), followed by sore throat in 22.6% (95% CI, 0.078-0.502), dyspnea in 15.7% (95% CI, 0.067-0.328), and diarrhea in 15.6% (95% CI, 0.075-0.295). Reflecting the young age of the patients, 19.7% reported having at least one coexisting medical condition, such as gestational diabetes mellitus, hypothyroidism, hypertension, hepatitis B virus infection, and autoimmune disease.
An elevated neutrophil count was reported in 67.8% of the patients (95% CI, 0.478-0.829), with lymphocytopenia present in 50% (95% CI, 0.331-0.669). C-reactive protein and D-dimer levels were elevated in most patients as well. All patients (n = 136) had a chest computed tomography (CT) scan done on admission, which showed abnormalities in 98% of cases. Ground-glass opacities were the most common finding (81.7%; 95% CI, 0.701-0.895), followed by shadow infiltrates, which were present in 42.5% of cases (95% CI, 0.126-0.791).
Most of the mothers had cesarean deliveries (76.3%; 95% CI, 0.658-0.842). Eighty-seven percent received antibiotic therapy (95% CI, 0.775-0.943), 67.5% received antiviral therapy (including some who received oseltamivir [95% CI, 0.484-0.821]), and 50.5% received steroids (95% CI, 0.285-0.723). The investigators did not report outcomes for these treatments between patients who received them and those who did not. Furthermore, no specific data on remdesivir were presented.
Thirty-seven percent of the newborns were delivered preterm (95% CI, 0.269-0.500), two tested positive for COVID-19 (both were delivered by cesarean), and three died. Two of the deaths were attributed to multisystem organ failure with disseminated intravascular coagulation, while one had an Apgar score of 0 and died immediately after delivery. Amniotic fluid, placenta fluid, umbilical cord, and gastric fluid tested negative for COVID-19 in all patients.COMMENTARY
The report by Matar and colleagues is valuable because it presents clinical details about two patient populations that have been understudied during the COVID-19 pandemic: pregnant women and their offspring. Although correlation does not equal causality, the finding that COVID-19 infection during pregnancy leads to less favorable outcomes seems like a scientifically plausible hypothesis. This underscores the importance of pregnant women avoiding COVID-19, and all of the currently available strategies (e.g., social distancing, hand washing, avoiding crowds, and vaccination) to achieve this goal should be encouraged strongly. Indeed, regarding vaccines, the Centers for Disease Control and Prevention currently recommends that pregnant women should talk to their healthcare providers to make an informed decision.1 There is no evidence that antibodies formed from COVID-19 vaccination cause any problem during pregnancy, including the development of the placenta, yet data do exist that COVID-19 is a serious threat to both the mother and her baby.
The study has a number of limitations. One is that it analyzed data collected from Dec. 1, 2019, to April 30, 2020, so that it might not reflect outcomes in women infected with the more recently emerged variants of SARS-CoV-2. Another is the relatively young age of the mothers, which was 25 to 34 years. Older and younger mothers may have had different outcomes, particularly older mothers with presumably more underlying health conditions. Furthermore, since most of the included studies were conducted in China (20/24), they might not be representative of other geographic areas. Finally, all of the participants were hospitalized; thus, the findings might not apply to pregnant women in the ambulatory setting.
Obstetricians must appreciate the danger posed by COVID-19 to their patients and take aggressive measures to mitigate the threat. Furthermore, vaccination for pregnant women should be recommended unless there are extenuating circumstances, e.g., allergic reaction to the vaccine. It is hoped that the emergence of new data will lead to improved outcomes for pregnant women and their offspring.