key: cord-0711139-6vh9kboy
authors: Sahin, Dilek; Tanacan, Atakan; Erol, Seyit Ahmet; Yucel Yetiskin, Fatma Didem; Besimoglu, Berhan; Ozden Tokalioglu, Eda; Anuk, Ali Taner; Turgut, Ezgi; Goncu Ayhan, Sule; Turgay, Batuhan; Unlu, Serpil; Kanmaz, Gozde; Dinc, Bedia; Ozgu‐Erdinc, A. Seval; Keskin, Huseyin Levent; Surel, Aziz Ahmet; Moraloglu Tekin, Ozlem
title: Management of pregnant women with COVID‐19: A tertiary pandemic center experience on 1416 cases
date: 2021-11-02
journal: J Med Virol
DOI: 10.1002/jmv.27423
sha: 473fdefdba1a95bfb94f2a0951e87e73c55de4c2
doc_id: 711139
cord_uid: 6vh9kboy

The aim of this study is to share the comprehensive experience of a tertiary pandemic center on pregnant women with COVID‐19 and to compare clinical outcomes between pregnancy trimesters. The present prospective cohort study consisted of pregnant women with COVID‐19 who were followed up at Ankara City Hospital between March 11, 2020 and February 20, 2021. Clinical characteristics and perinatal outcomes were compared between the pregnancy trimesters. A total of 1416 pregnant women (1400 singletons and 16 twins) with COVID‐19 were evaluated. Twenty‐six (1.8%) patients were admitted to the intensive care unit (ICU) and maternal mortality was observed in six (0.4%) cases. Pregnancy complications were present in 227 (16.1%) cases and preterm labor was the most common one (n = 42, 2.9%). There were 311, 433, and 672 patients in the first, second, and third trimesters of pregnancy, respectively. Rates of mild and severe/critic COVID‐19 were highest in the first and second trimesters, respectively. The hospitalization rate was highest in the third trimester. Pregnancy complications, maternal mortality, and NICU admission rates were similar between the groups. The course of the disease and obstetric outcomes may be different among pregnancy trimesters. A worse course of the disease may be observed even in pregnant women without any coexisting health problems.

the data in the current literature indicate that the disease may be more severe in pregnant women and may lead to increased obstetric complications. [5] [6] [7] [8] Our knowledge of the selection of appropriate medications, follow-up of pregnancy, management of severe COVID-19 cases, the timing of delivery, and vertical transmission is still limited. [9] [10] [11] [12] Furthermore, there are few studies investigating the effect of pregnancy trimesters on the clinical course and complications of the disease. [13] [14] [15] For this reason, experiences of pandemic centers dealing with many patients are crucial to provide better healthcare for the patients.

The present study aims to share the comprehensive experience of a tertiary pandemic center on pregnant women with and to compare clinical outcomes of pregnancy trimesters. This study is the latest update of the previous two studies by Sahin et al. 16, 17 In the first part of the study, demographic features, clinical characteristics, medications, initial laboratory test results, and perinatal outcomes of all patients were reported. Maternal age, gravidity, parity, living child, previous miscarriage, prepregnancy body mass index (BMI), route of admission to hospital, comorbid diseases, gestational age at diagnosis, pregnancy trimester at diagnosis, initial symptoms, close contact with a confirmed or suspected case, abnormal vital signs at admission to hospital, pregnancy-specific medications, COVID-19 medications, antibiotherapy for other pathogens, respiratory support, intensive care unit (ICU) admission, maternal mortality rate, hospitalization rate, length of hospital stay, complete blood cell count, serum biochemistry values, radiologic imaging, blood groups, pregnancy complications, delivery status, time interval between diagnosis and delivery, route of delivery, cesarean section indications, labor anesthesia, spontaneous labor rate, frequency of preterm deliveries, gestational age at delivery, birth weight, 1st and 5th minute Apgar scores, neonatal intensive care unit (NICU) admission rates and vertical transmission were all recorded. Afterward, maternal mortality cases with COVID-19 were evaluated. Finally, clinical characteristics and perinatal outcomes were compared between the pregnancy trimesters. The management of all cases was performed by a multidisciplinary and highly experienced team considering the current guidelines. 11, 12, 18 The severity of COVID-19 was assessed according to the national guideline. 18 All physical, ultrasonographic examinations and deliveries were performed using necessary personal protective equipment. 19 Statistical analyses were performed using the Statistical Package Descriptive analyses were presented as means and standard deviations. As continuous variables were normally distributed, the oneway analysis of variance or Student's t tests were performed to compare the mean values among the groups. Posthoc analysis with the Tukey test was performed to assess the significance of pairwise differences using the Bonferroni correction to adjust for multiple

comparisons. An overall 5% type-I error level was used to infer statistical significance. Categorical data were presented as percentages.

Chi-square test was used to compare categorical variables among the groups. A two-tailed p < 0.05 was regarded as statistically significant. 20 However when the placenta, umbilical cord blood, amniotic fluid, and vaginal secretions of the mother whose neonate was positive were evaluated, all theall the samples were found to be negative for SARS-CoV-2.

Clinical characteristics of maternal mortality cases with COVID-19 were summarized in Table 4 . Only one patient had the comorbid disease (obesity). There were one, two, and three patients in the first, second, and third trimesters, respectively. One patient had severe and the remaining patients had critic COVID-19 at admission. All patients had oxygen saturation ≤93% upon admission to the hospital. 

Appropriate management of pregnancy during the COVID-19 pandemic is a challenging issue as pregnant women have higher risks for the worse clinical course of the disease and increased rates of pregnancy complications. [5] [6] [7] There are also controversial issues regarding the efficacy of medications, the optimal route of delivery, the safety of breastfeeding, and the risk of vertical transmission. [9] [10] [11] [12] Moreover, there is not enough information in the literature related to the course and possible adverse effects of COVID-19 in different pregnancy trimesters. [13] [14] [15] Thus, cumulative knowledge of the prognosis and perinatal outcomes of pregnant women with COVID-19 is important to establish better clinical protocols. 16, 17 To the best of our knowledge, the present study is the largest series presented from a single center and is one of the few studies examining pregnancy trimesters. [13] [14] [15] Nearly a quarter of patients had comorbid conditions in the present study and the most common of them was obesity. It has been long known that individuals with chronic diseases have a higher risk for severe illness and mortality. 21, 22 Yet, more than 90% of cases had mild disease and only 2% were admitted to NICU. These findings were most probably due to the younger age of the study population.

On the other hand, only one patient had comorbidity among the maternal mortality cases. Therefore, physicians should keep in mind that the worse course of the disease may be observed even in pregnant women without any coexisting health problems.

According to the results of a report including a large population of patients from the United States, approximately 90% of cases were symptomatic at hospital admission. Cough, headache, myalgia, and fever were the most common clinical findings reported in the infected pregnant women. 23 Forty percent of the cases in the present study were asymptomatic. Cough, myalgia, and dyspnea were the most frequent initial symptoms. Although these results were relatively consistent with the literature, the number of asymptomatic cases was higher than the current report most probably due to the high number of screening tests performed by the national filiation teams. 23 Another important topic is the administration of pregnancyspecific medications, International societies recommend the application of routine antenatal medication protocols like tocolysis and antenatal corticosteroids in necessary conditions as far as the patient's condition allows. 11, 12 Tocolytic agents were rarely used in the present study and antenatal corticosteroids were only administered in 5% of the cases.

Specific therapy for COVID-19 was given to more than half of the cases in the present study. Some studies investigated the relationship between ABO blood types and COVID-19. However, they reported controversial results and the clinical implication of ABO blood types in the management of COVID-19 is not clear. 30, 31 A and 0 Rh+ were the most common blood types in the present study.

Higher rates of obstetric complications were reported in pregnant women with COVID-19. [5] [6] [7] [8] Excessive inflammatory response, hypoxia, impaired cytokine production, and coagulation disorders associated with COVID-19 were all considered as the possible pathophysiological events behind poor obstetric outcomes in infected cases. 32, 33 Pregnancy complications were observed in 16% of the cases and preterm labor was the most common one followed by been identified yet, most of the studies reported increased rates of preterm delivery. 34, 35 Another hot topic in pregnant women with COVID-19 is choosing the optimal route of delivery. Although the cesarean section was the preferred method in the early period of the pandemic, the current trend is to choose the route of delivery according to obstetric indications. 11, 12 Cesarean section was performed in approximately two-thirds of the cases in the present study and previous cesarean section was the most common indication followed by fetal distress. Only 5% of the cesarean section deliveries were performed due to maternal health conditions. These results were consistent with the literature. 35, 36 Regional anesthesia was the preferred method and the majority of the labors had started spontaneously.

Although some studies indicated convincing results for the vertical transmission of COVID-19, no consensus could be reached on this issue. 37 One case of neonatal SARS-CoV-2 positivity was observed in the present study and viral RNA was detected only in one breast milk sample. 20 Although the NICU admission rate was relatively high, all were due to prematurity or neonatal respiratory distress.

In the present study, the rate of asymptomatic cases was lower, and severe/critical cases were higher in the second trimester compared to the other trimesters. The hospitalization rate was highest in the third trimester, most probably due to the concerns of the physicians. Length of hospital stay was lowest in the first trimester and radiologic imaging findings were highest in the third trimester. In our opinion, high rejection rates for radiologic imaging in the early trimesters might be the reason for these findings. Cesarean section rate was highest in patients diagnosed in the third trimester, most probably due to maternal reasons. Mean birth weight was lowest in the second-trimester cases. However, the mean gestational age at birth was similar between the groups. Maternal mortality, obstetric complication, and NICU admission rates were comparable between the groups.

Although there are studies in the literature focusing on pregnancy trimesters and COVID-19, to the best of our knowledge present study is the most comprehensive research investigating the outcomes of pregnant women diagnosed at different trimesters. [13] [14] [15] Recent studies underlined the severe course of COVID-19 in pregnant women. Pregnant women with SARS-CoV-2 infection have higher risks for ICU admission, invasive ventilation, and maternal mortality. 38, 39 For this reason, effective clinical management protocols should be established by a multidisciplinary medical team to prevent pregnant women from COVID-19 related fatal complications. 40 Vaccination of pregnant women against SARS-CoV-2 was reported to be associated with favorable outcomes. 41, 42 Although many pregnant women are still reluctant to get vaccinated, vaccination is an effective and safe protective measure in these special populations. 43 Therefore, vaccination should be encouraged by healthcare professionals and immunization programs should be organized by the states.

The main strengths of the present study were the large number of cases, prospective design, and the high number of study parameters. Moreover, a comparison of patients diagnosed at different pregnancy trimesters was the other important part. On the other hand, the lack of information related to the long-term outcomes of the cases was the main limitation.

In conclusion, an individualized approach should be provided to pregnant women with COVID-19, and management of these cases should be performed within the framework of a multidisciplinary team.

Special thanks to all the health care staff of our hospital who work devotedly for the health of our community during the pandemic period.

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Management of pregnant women with COVID-19: a tertiary pandemic center experience on 1416 cases

The authors declare that there are no conflict of interests. h Pairwise comparisons revealed significant differences between first and second trimesters (p = 0.02).

All the authors cited in the manuscript had substantial contributions to the concept and design, the execution of the work, or the analysis and interpretation of data; drafting or revising the manuscript, and have read and approved the final version of the paper. Dilek Sahin:Conceptualization, methodology, visualization, reviewing, and editing.