key: cord-0804822-7f22u4wl authors: Samadi, Parisa; Alipour, Zahra; Ghaedrahmati, Maryam; Ahangari, Roghayeh title: The severity of COVID‐19 among pregnant women and the risk of adverse maternal outcomes date: 2021-04-26 journal: Int J Gynaecol Obstet DOI: 10.1002/ijgo.13700 sha: bb2b05c0a5b740b7d56ccb2e28ae7ba2e90317b5 doc_id: 804822 cord_uid: 7f22u4wl OBJECTIVE: To evaluate the relationship between the severity of coronavirus disease 2019 (COVID‐19) during pregnancy and the risk of adverse maternal outcomes. METHODS: A descriptive‐analytical cross‐sectional study conducted on 258 pregnant women who were hospitalized due to confirmed COVID‐19 from March 2020 to January 2021 at the Forghani Hospital in Qom, Iran. Demographic and obstetric characteristics, laboratory findings, and adverse maternal outcomes were recorded from the patients’ medical records. The Fisher exact test, one‐way analysis of variance, and regression logistics were used to assess the relationship between variables. RESULTS: Of the total study population, 206 (79.8%) pregnant women had mild to moderate disease, 43 (16.7%) had severe disease, and 9 (3.5%) were in the critical stage of the disease. Eight women (3.1%) died and 33 (12.8%) were admitted to the intensive care unit (ICU). The most important demographic factors associated with the severity of the disease were ethnicity, underlying conditions, maternal age, and parity. The severity of the disease was significantly associated with increased cesarean delivery and admission to the ICU. CONCLUSION: Pregnant women with severe and critical disease had a high rate of cesarean delivery and admission to the ICU. There were eight cases of maternal mortality. | 93 SAMADI et Al. and physiological cardiopulmonary changes (diaphragm elevation, increased consumption of oxygen, and respiratory tract mucosal edema). 8 Therefore, pregnant women are a vulnerable population, and there are many challenges to deciding how to deal with, prevent, and treat infectious diseases. 9 Studies in pregnant women on other coronavirus epidemics, such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), have also been associated with increased maternal morbidity, mortality, and adverse pregnancy and delivery outcomes. The influenza pandemic of 1918 killed 2.6% of the total population, but the mortality rate for pregnant women was 37%. 10 Regarding the relationship between COVID-19 and pregnancy outcomes, the results of a systematic review showed that 69.4% were delivered by cesarean section and 30.6% by vaginal delivery. Out of 256 newborns, four were positive on reverse transcriptase-reverse polymerase chain reaction (RT-PCR) test and there were two stillbirths and one neonatal death. 3 Maternal complications such as severe pneumonia also occurred in 14% of pregnant women, and most cases required admission to the intensive care unit (ICU) and invasive mechanical ventilation, with one reported maternal death. 4 Given that viral epidemics threaten the general population, including pregnant women, and pregnancy is a unique immune condition that is modulated but not suppressed, 9 and given that there are still many unanswered questions about the clinical course of COVID-19 in pregnant women, [5] [6] [7] understanding the correct concept of the severity of coronavirus disease in pregnancy and its impact on pregnancy and childbirth outcomes allows caregivers and policymakers to make valid recommendations for the treatment of pregnant women during the coronavirus pandemic. Therefore, the aim of the present descriptive-analytical crosssectional study was to evaluate relationship between the severity of COVID-19 during pregnancy and adverse maternal outcomes. A descriptive-analytical cross-sectional study was conducted on women who were at 5-42 weeks of pregnancy who were hospital- In the present study, the inclusion criteria were all women at 5-42 weeks of pregnancy who had COVID-19 confirmed by viral RNA detection in a PCR test or the presence of marked changes in computed tomography (CT) scans of the lungs or both. Data collection was performed by a reproductive health specialist . The demographic characteristics of pregnant women with COVID-19 and history of underlying diseases such as gestational diabetes, chronic diabetes, chronic hypertension and pre-eclampsia, kidney and liver disease, cancer, and body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) were recorded according to the patients' medical records. Gestational age was also calculated based on the ultrasound reported in the patients' medical records. Drugs used to treat COVID-19, including hydroxychloroquine, azithromycin, ceftriaxone, or other research drugs (e.g. RemedSiver and plasma injections) were recorded from the patients' medical records. In addition, laboratory findings such as lymphopenia, leukopenia, thrombocytopenia, erythrocyte sedimentation rate, concentration of C-reactive protein (CRP), alanine aminotransferase, aspartate aminotransferase, white blood cell count, and concentration of hemoglobin were recorded from the patients' medical records. Pregnancy and childbirth outcomes include: rate of abortion, prolonged labor, method of delivery (normal vaginal delivery, emergency cesarean delivery due to fetal distress, emergency cesarean delivery due to complications of COVID-19 in the mother); postpartum complications such as placental abruption, abscess at the site of a cesarean delivery or episiotomy, hematoma, and postpartum hemorrhage. In addition, length of hospital stay, duration of hospitalization in the ICU, and maternal deaths were recorded according to the patients' medical records. Information was obtained through telephone interviews if some of the required information was not included in a patient's medical records. The severity of COVID-19 in pregnancy was classified according to the guidelines of the Society for Maternal and Fetal Medical Association as follows: mild illness was categorized by symptoms such as fever, fatigue, cough, and the less common features of COVID-19; severe illness was categorized as tachypnea (respiration rate >30 breaths per minute), hypoxia (oxygen saturation in room air of 93% or PaO 2 /FiO 2 <300 mm Hg), or >50% lung involvement on imaging; and the critical stage of the disease was characterized by respiratory failure, shock, or the dysfunction of several organs. 11, 12 Other studies also categorized the clinical manifestations from mild to severe and critical. 3 In a systematic review, the severity of disease in pregnant women was also as reported mild, severe, and critical. 4 In the present study, all pregnant women were hospitalized with symptomatic COVID-19; therefore, asymptomatic individuals were not included in the study. To define severe COVID-19 in the present study, "dyspnea" was defined as shortness of breath reported by the patient at rest. The critical stage of COVID-19 was defined as respiratory failure requiring mechanical ventilation, septic shock, or dysfunction or multiple organ failure. 13, 14 Respiratory failure is also defined as the need for invasive mechanical ventilation. 15 The sample size in the present study, according to a similar study 15 and based on α = 0.05 and β = 0.1, was 120 people and the sample size was increased according to the period and spread of disease to increase the accuracy of the study. In the present study, the χ 2 test, Fisher exact test, and one-way analysis of variance (ANOVA) were used to assess the relationship between demographic characteristics, obstetrics, and laboratory findings with the severity of COVID-19, and the relationship between disease severity and pregnancy and childbirth outcomes (Tables 1-3) . Regression logistics were used to examine the predictors of adverse pregnancy outcomes, which were two-state, and confounding variables simultaneously entered into regression analysis. These relationships were adjusted for ethnicity, maternal age, underlying disease, and severity of COVID-19 ( Table 1 ). The results showed that maternal BMI and parity were significantly associated with disease severity (P = 0.05), and mothers with higher BMI and multiparity may develop more severe coronavirus disease. The results showed that ethnicity and underlying conditions of pregnant women were significantly associated with an increased risk of severity of disease (Table 1) . Regarding the relationship between the severity of coronavirus disease in pregnancy and laboratory findings, the results of the ANOVA are reported in Table 2 . The results of the ANOVA showed that the mean length of stay in hospital and hospitalization in the ICU of pregnant women with COVID-19 were significantly different between the three groups in terms of severity of disease (P = 0.001). The results showed that with the increasing severity of disease, the probability of the length of stay in hospital and hospitalization in the ICU increased (P = 0.001) ( Table 4 ). In the study of the relationship between the severity of coronavirus disease and delivery outcomes, the results of the χ 2 test showed that the severity of the disease is significantly associated with cesarean delivery (P = 0.001). Logistic regression for qualitative variables was used to investigate the factors predicting adverse maternal outcomes. In the present study, the variables of maternal age, ethnicity, underlying diseases, and severity of COVID-19 were entered into the test simultaneously as confounding variables in the severity of COVID-19. After adjusting the confounding variables, the only factor that was effective in increasing the rate of cesarean delivery was the severity of coronavirus disease (odds ratio 16.3, 95% confidence interval 3.04-87.25) (P < 0.001). A descriptive-analytical cross-sectional study was performed on 258 pregnant women with confirmed SARS-CoV-2 infection: 79.8% had mild to moderate disease; 16.7% had severe disease; and 3.5% were critical. Of the women, 12.8% were admitted to the ICU and 3.1% died. In other studies, clinical manifestations ranged from mild in 81% to severe disease in 14%, and the critical stage was reported in 5%; the mortality rate was 2.3%. 3 The most common clinical symptoms reported by pregnant women with COVID-19 were dry cough, shortness of breath, fever, muscle aches, and headache. "It was noted that some clinical manifestations of COVID-19 overlapped with symptoms of pregnancy (e.g. fatigue, shortness of breath, nasal congestion, nausea/vomiting), so these should be considered in the evaluation of pregnant women". 16 In the present study, the most important demographic factors associated with the severity of disease were Afghan ethnicity, underlying conditions, maternal age, and parity. Labratory findings also showed that in severe and critical cases of the disease, lymphopenia occurred and liver enzymes increased significantly. In addition, maternal outcomes that had a significant relationship with the severity of disease were increase in cesarean delivery and admission to the ICU. Other studies have reported that the proportion of pregnant women of different ethnicities, such as black and Hispanic women with COVID-19, was higher than the overall proportion of pregnant women aged 15-49 years. [17] [18] [19] The results of other studies show that racial and ethnic differences increased both the risk of infection and the risk of severity of COVID-19 in pregnant women, which may indicate the need to address potential risk factors such as long-term inequalities in social health factors such as employment and housing conditions, and social distance in these populations. 17 In terms of the relationship between laboratory findings and the severity of COVID-19, the results of the present study showed that a decrease in the levels of lymphocytes and an increase in liver enzymes and CRP were significantly associated with disease severity. Other studies reported that 35% of pregnant women with COVID-19 had lymphopenia and increased CRP. 16, 20 Evidence suggests that viral infections may cause a syndrome known as secondary lymphohistiocytosis. It has also shown that patients with severe and critical COVID-19 may develop cytokine syndrome, and that patients with severe COVID-19 who develop hypercytokinemia and multiple organ failure ultimately die. 3 The results of the present study also showed that 77.8% of people who were in the critical stage of the disease developed lymphopenia and died. In examining the relationship between the severity of coro- 15 The results of other systematic reviews showed that 86% and 69.4% of pregnant women with COVID-19 were delivered by cesarean section. 3, 21 In the present study, 3.1% of the mothers died. The strengths of the present study are that only pregnant women with confirmed COVID-19 infection by CT scan or PCR or both were included in the study. In addition, because patients were divided into three groups, it was possible to compare maternal outcomes according to the severity of the disease. One of the limitations of the present study was that less than half of the pregnant women gave birth during this period and the delivery outcomes of many infected women were not available. Further, due to the lack of access to some medical records, not all pregnant women with COVID-19 were examined during pregnancy. The most important demographic factors related to the severity of disease were ethnicity, underlying conditions, maternal age, and parity. Adverse outcomes such as admission to the ICU and the need for cesarean delivery occurred in pregnant women with severe COVID-19. The researchers sincerely thank the Research Deputy, Midwifery, The authors have no conflicts of interest. Director-General's Opening Remarks at the Media Briefing on COVID-19 WHO Health Emergency Dashboard. WHO Coronavirus Disease (COVID-19) Dashboard. Data last updated: 2021/2/11 A systematic scoping review of COVID-19 during pregnancy and childbirth Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review Severity of COVID-19 in pregnancy: a review of current evidence Clinical Management of Severe Acute Respiratory Infection when Novel Coronavirus (2019-nCoV) Infection is Suspected: Interim Guidance Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study Potential maternal and infant outcomes from (Wuhan) coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and other human coronavirus infections The immune system in pregnancy: a unique complexity Coronavirus disease 2019 in pregnant women: a report based on 116 cases Mild or moderate covid-19 Management considerations for pregnant patients with COVID-19 COVID-19) treatment guidelines Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 72 314 cases from the Chinese Center for Disease Control and Prevention Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study Coronavirus Disease 2019 (COVID-19): Pregnancy Issues and Antenatal Care Characteristics and maternal and birth outcomes of hospitalized pregnant women with laboratory-confirmed COVID-19 -COVID-NET Update: Characteristics of symptomatic women of reproductive age with laboratoryconfirmed SARS-CoV-2 infection by pregnancy status -United States Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis Coronavirus in pregnancy and delivery: rapid review The severity of COVID-19 among pregnant women and the risk of adverse maternal outcomes