The impact of coronavirus disease 2019 (COVID-19) on the perioperative outcomes of emergency cesarean section in maternal and neonatal prognosis: A propensity score-matched analysis

doi:10.21203/rs.3.rs-4842485/v1

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Research Article

The impact of coronavirus disease 2019 (COVID-19) on the perioperative outcomes of emergency cesarean section in maternal and neonatal prognosis: A propensity score-matched analysis

https://doi.org/10.21203/rs.3.rs-4842485/v1

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Objective

To evaluate the impact of COVID-19 infection on maternal and neonatal prognosis.

Study Design and Setting:

This retrospective, propensity score-matched analysis was conducted at Beijing Tiantan Hospital, China, from October 2022 to December 2022.

Participants:

We retrospectively collected clinical data from 711 parturient women and their neonates. The inclusion criteria were: 1) parturient women who underwent emergency caesarean section within less than 2 hours; 2) parturient women who underwent nucleic acid testing for COVID-19; and 3) at least one COVID-19 related clinical symptom, such as fever, cough, nausea, or other symptoms. The exclusion criteria were parturient women who had natural childbirth or lacked COVID-19 related clinical symptoms.

Methods

Propensity score matching (PSM) was performed based on whether the parturient women were infected with COVID-19 (defined as nucleic acid test positive combined with at least one clinical symptom related to COVID-19 infection, versus test negative). The covariates included age, height, weight, Body Mass Index (BMI), weight gain during pregnancy, anesthesia method, gestational week, term pregnancy, preoperative routine blood test, and coagulation function.

Results

The research cohort ultimately included 58 parturient women and their newborns through PSM and inverse probability of treatment (n = 29 positive, n = 29 negative). There was a lower incidence of fetal distress in the non-infected group (17.24% vs 44.83%, OR = 3.9, 95% CI 1.163–13.078, P = 0.023). The anesthesia satisfaction score and postoperative recovery quality (QoR-15) score were higher in the non-infected group (10 vs 10, P = 0.005 and 144 vs 148, P = 0.029, respectively).

Conclusion

COVID-19 infection combined with related clinical symptoms may increase the likelihood of fetal distress and reduce maternal satisfaction with anesthesia and postoperative recovery quality scores.

COVID-19

infection

emergency cesarean section

newborn

maternal prognosis

The COVID-19 virus and the measures taken in response have had a profound impact on human health, society, and the global economy, with China being no exception[1]. In areas with widespread community transmission, healthcare personnel are required to implement preventive measures to reduce potential exposure. Additional protective measures are necessary for suspected or confirmed COVID-19 patients[2]. As China began to gradually adjust its "zero-tolerance" policy at the end of 2022[3, 4], the number of positive cases, including pregnant women, increased dramatically. However, during the early stages of the COVID-19 pandemic, there were limited reports on the impact of the virus on pregnant women and newborns[5].

Caesarean section is one of the most common and important surgical procedures performed in operating rooms in China and many other countries worldwide. The consensus among experts in caesarean section surgery in China aligns with the guidelines issued by the National Institute for Health and Care Excellence (NICE) and the American College of Obstetricians and Gynecologists (ACOG). However, it is recommended to determine the medical indications for caesarean section based on thorough individual assessments. Newly diagnosed pregnant women with COVID-19 may meet the indications for caesarean section surgery in cases where there is evidence of fetal distress or when there is a heightened risk of intrapartum transmission due to maternal infection[6]. Therefore, we conducted a retrospective cohort study of COVID-19 positive and negative pregnant women who underwent emergency caesarean section at Beijing Tiantan Hospital between October and December 2022, aiming to provide reliable clinical data on perioperative outcomes for COVID-19-positive parturient women and neonates.

Study Design and Data Source

The data source for this retrospective cohort study was the database of parturient women who underwent emergency caesarean section during COVID-19 at Beijing Tiantan Hospital affiliated with Capital Medical University. The database collected data, including nucleic acid detection results for COVID-19 and related clinical symptoms of parturient women, from October 2022 to December 2022, before the emergency caesarean section to 30 days of post-operation. The quality and reliability of the data were ensured by two professionally trained research assistants, who conducted strict data entry and dual checks.

Patient Population

We identified parturient women who underwent emergency caesarean sections from October 2022 to December 2022. The inclusion criteria were as follows: 1) the duration of the emergency caesarean section was less than 2 hours; 2) the parturient women were tested for COVID-19 nucleic acid detection; and 3) at least one COVID-19-related clinical symptom was present, including dry throat, sore throat, cough, fever, muscle soreness, loss of smell or taste, nasal congestion, runny nose, diarrhoea, conjunctivitis, pneumonia, dyspnoea, and/or hypoxaemia. The exclusion criteria were parturient women who had natural childbirth or did not exhibit COVID-19-related clinical symptoms.

Baseline Characteristics

Data on baseline demographic characteristics and comorbidities were recorded, including age, height, weight, BMI, weight gain during pregnancy, anesthesia method, gestational weeks, full-term pregnancy, preoperative routine blood tests, and coagulation function. The results of the COVID-19 nucleic acid test were dichotomised into Yes or No.

Outcomes

Perioperative maternal and neonatal prognosis and outcomes were assessed. These included the presence of fetal distress before the operation, Apgar scores of the newborns, growth and development indicators of the newborns, outcomes 30 days after birth, the impact of COVID-19 on lactation, the feeding mode of the newborns, COVID-19 infection status of the newborns, whether the parturient women required blood transfusion (intra- or postoperative), routine blood examination of the parturient women post-operation, anesthesia satisfaction scores, blood loss, infusion volume, QoR-15 score[7], and length of hospital stay.

Statistical Analysis

Due to the limited number of positive maternal cases in this research center, the inverse probability of treatment weighting method was adopted to minimise sample size loss during matching. Therefore, the sample size of this study was not accurately calculated.

Propensity scores were calculated using logistic regression, with COVID-19 status (nucleic acid tested positive and exhibiting at least one clinical symptom related to COVID-19 infection defined as positive; tested negative defined as negative) as the treatment indicator and age, BMI, weight gain during pregnancy, anesthesia method, full-term pregnancy, preoperative routine blood test, and coagulation function as covariates (independent variables). Propensity score matching was performed in a 1-to-1 ratio using the K-nearest neighbour technique to generate two cohorts (positive vs. negative), adjusted for the specified baseline covariates.

Descriptive statistics included counts and percentages for categorical variables, and means and standard deviations for continuous variables. Baseline characteristics in the positive and negative pregnant women of the propensity score-matched cohorts were compared using the chi-square or Fisher’s exact test for categorical variables and Student's two-sample t-test for continuous variables. Normality was assessed using Shapiro–Wilk tests. For continuous normally distributed data, Student's two-sample t-test was used to compare mean differences. Non-normal data were analysed with the Mann–Whitney U test. Categorical data were reported as frequencies (percentages) and analysed using the χ2 test.

The threshold for statistical significance was set a priori at P = 0.05 (two-tailed). All statistical analyses were performed using Python version 3.11.3.

Ethics Approval

The study was reviewed and approved by the Ethics Committee of Beijing Tiantan Hospital of Capital Medical University (2010L02820).

We collected clinical data from 711 parturient women at Beijing Tiantan Hospital from October to December 2022. After applying the inclusion and exclusion criteria, 44 of these women tested positive for COVID-19 and underwent caesarean section. The research cohort eventually included 58 parturient women and their newborns through propensity score matching and inverse probability of treatment. Twenty-nine of the women were COVID-19 positive, and 29 were negative. Figure 1 shows the distribution of propensity scores before and after matching. Maternal baseline characteristics of the study cohort are presented in Table 1. There were no statistically significant differences in age, height, weight, BMI, weight gain during pregnancy, anaesthesia method, gestational week, term pregnancy, preoperative routine blood test, and coagulation function between the positive and negative groups.

Table 1

Maternal baseline characteristics of the study cohort
	Total (n = 58)	Positive^# (n = 29)	Negative^@ (n = 29)	P value
Mean age (yr)	31.3 ± 3.6	30.4 ± 3.5	32.2 ± 3.6	0.057
Height (cm)	163 ± 5	163 ± 5	163 ± 5	0.828
Weight (kg)	72 ± 10	72 ± 11	73 ± 9	0.583
BMI(kg/m²)	27.2 ± 3.4	26.9 ± 3.8	27.5 ± 3.1	0.489
Weight gain during pregnancy(kg)	14 (10, 16.6)	12 (10, 17)	14 (11.5, 16.25)	0.221
Gestational week(week)	38.5 ± 1.4	38.3 ± 1.3	38.7 ± 1.4	0.29
Type of anaesthesia(n, %)				1.000
Intraspinal anaesthesia	56(96.6)	28 (96.6)	28 (96.6)
General anaesthesia	2 (3.4)	1 (3.4)	1 (3.4)
Preoperative coagulation function
Prothrombin time (PT, sec)	10.2 (9.8, 10.5)	10.2 (9.8, 10.6)	10.2 (9.7, 10.4)	0.354
Activated partial thromboplastin time (APTT, sec)	27.1 (25.9, 28.9)	28.5 (26.4, 29.2)	26.7 (25.8, 28.3)	0.072
International normalized ratio (INR)	0.93 (0.89, 0.96)	0.93 (0.89, 0.96)	0.93 (0.88, 0.95)	0.410
Fibrinogen (Fbg, g/L)	4.6 ± 0.9	4.5 ± 1.1	4.6 ± 0.8	0.692
Thrombin (TT, sec)	13.5 ± 0.7	13.6 ± 0.7	13.5 ± 0.8	0.56
Preoperative blood routine
Leukocyte (10⁹/L)	10.0 (7.9, 12.8)	9.9 (8.1, 11.8)	10.6 (7.33, 13.4)	0.715
Hematocrit (%)	0.35 ± 0.03	0.35 ± 0.03	0.35 ± 0.03	0.945
Platelet (10⁹/L)	173 (144, 204)	164 (145, 198)	183 (140, 219)	0.263
# means maternal nucleic acid tested positive and combined with at least one of the clinical symptoms related to COVID-19 infection, such as dry throat, sore throat, cough, fever, muscle soreness, loss of smell or taste, nasal congestion, runny nose, diarrhea, conjunctivitis, pneumonia, dyspnea and/or hypoxemia.
@ means maternal nucleic acid tested negative.

Maternal outcomes are summarized in Table 2. The positive group had similar intraoperative blood loss volume (450 ml vs 450 ml), intraoperative fluid infusion volume (500 ml vs 500 ml), blood transfusion volume (0 ml vs 0 ml), length of stay (4 days vs 4 days), postoperative leukocyte count (9.17 × 10⁹/L vs 10.54 × 10⁹/L), haematocrit (0.33 vs 0.34), and platelet count (157 × 10⁹/L vs 166 × 10⁹/L) compared to the negative group. However, the anesthesia satisfaction score and postoperative QoR-15 score of the negative group were higher (10 vs 10, P = 0.005 and 144 vs 148, P = 0.029, respectively).

Table 2

Maternal outcomes of the study cohort (n = 58)
	Positive^# (n = 29)	Negative^@ (n = 29)	P value
Anaesthesia Satisfaction Score	10 (8, 10)	10 (10, 10)	0.005
Blood Loss (ml)	450 (450, 450)	450 (450, 450)	0.563
Fluid Infusion Quantity (ml)	500 (500, 1000)	500 (500, 1000)	0.709
Transfusion (ml)	0 (0, 0)	0 (0, 0)	1.000
Length of Stay hospital (days)	4 (3, 4)	4 (3, 4.5)	0.485
Recovery Score	144 (140, 148)	148 (144, 150)	0.029
Postoperative blood routine
Leukocyte (10⁹/L)	9.2 (7.0, 11.0)	10.5 (8.4, 12.2)	0.184
Hematocrit (%)	0.33 ± 0.04	0.34 ± 0.04	0.365
Platelet (10⁹/L)	157 (136, 176)	166 (140, 203)	0.456
# means maternal nucleic acid tested positive and combined with at least one of the clinical symptoms related to COVID-19 infection, such as dry throat, sore throat, cough, fever, muscle soreness, loss of smell or taste, nasal congestion, runny nose, diarrhea, conjunctivitis, pneumonia, dyspnea and/or hypoxemia.
@ means maternal nucleic acid tested negative.

Table 3 displays the neonatal outcomes. There was a significant difference in neonatal fetal distress between the two groups, with a lower incidence of fetal distress in non-infected newborns (17.24% vs 44.83%, OR = 3.9, 95% CI 1.163–13.078, P = 0.023). The Apgar score at 5 minutes after birth (10 vs 10), feeding mode, birth height (51 cm vs 52 cm), birth weight (3326.6 g vs 3356.2 g), weight-to-length ratio (6.5 vs 6.5), and percentile of neonatal development (50% vs 50%) were similar between the positive and negative groups. Unfortunately, the 30-day growth and development indicators of the non-infected group were lost to follow-up.

Table 3

Neonatal outcomes of the study cohort (n = 58)
	Positive^# (n = 29)	Negative^@ (n = 29)	OR (95% CI) or MD (95% CI)	P
Fetal distress(n, %)			3.9 (1.163–13.078)	0.023
Yes	13 (44.83)	5 (17.24)
No	16 (55.17)	24 (82.76)
Apgar score	10 (10, 10)	10 (10, 10)	NA	0.666
Feed Pattern(n, %)			NA	0.097
Breast feeding	14 (48.23)	21 (72.4)
Bottle feeding	4 (13.8)	4 (13.8)
Mix	11 (37.9)	4 (13.8)
Growth and development indicators at birth
Weight (g)	3326 ± 363	3356 ± 442	29.7 (-183-242)	0.781
Height (cm)	51 (50, 53)	52 (50, 53)	NA	0.474
Newborn weight to length ratio	6.5 ± 0.6	6.5 ± 0.7	0.04 (-0.28-0.36)	0.811
Percentile Of Neonatal Develop (%)	50 (25, 75)	50 (25, 75)	NA	0.879
Growth and development indicators after 1month
Height (cm)	55.8 ± 2.6	NA	NA	NA
Weight (kg)	4654 ± 665	NA	NA	NA
Head circumference (cm)	38 (37, 38)	NA	NA	NA
# means maternal nucleic acid tested positive and combined with at least one of the clinical symptoms related to COVID-19 infection, such as dry throat, sore throat, cough, fever, muscle soreness, loss of smell or taste, nasal congestion, runny nose, diarrhea, conjunctivitis, pneumonia, dyspnea and/or hypoxemia.
@ means maternal nucleic acid tested negative.

As China began to gradually adjust its "zero-tolerance" policy, the number of positive COVID-19 cases surged dramatically by the end of September 2022, leading to an increase in the number of positive parturient women. At that time, there were no reliable data on the impact of the Omicron wave on maternal and neonatal outcomes[8, 9]. Our results indicated that neonatal fetal distress was higher, and maternal satisfaction with anesthesia and postoperative recovery quality scores were reduced among COVID-19-positive pregnant women during the perioperative period. However, it did not have a clear impact on neonatal growth and development indicators.

Studies have shown that parturient women infected with COVID-19, combined with related clinical symptoms, are prone to develop more severe infection symptoms. A meta-analysis comparing the clinical outcomes of COVID-19-positive pregnant women with non-pregnant women matched for age and sex showed that pregnancy increased the likelihood of severe monitoring, invasive ventilation, and extracorporeal membrane oxygenation, but did not increase the risk of death[10]. Another systematic review and meta-analysis on the impact of COVID-19 on pregnant women and newborns found that the virus significantly increased the rates of premature birth, preeclampsia, stillbirth, neonatal death, and maternal death[11, 12]. Consistent with previous studies, our results showed that the rate of neonatal fetal distress was higher among COVID-19-positive pregnant women during the perioperative period compared to those who were not infected[10, 13–16]. However, there was no significant difference between the two groups regarding other outcome indicators such as preeclampsia, stillbirth, neonatal death, and maternal death. This finding may be attributed to the short exposure time to COVID-19, the different viral strains in China, or the small sample size of our study during the data collection period. Differences in viral variants may explain the discrepancies in clinical outcomes during the perioperative period.

The present meta-analysis highlighted that the most common adverse outcome was fetal distress in newborns admitted to the NICU, which is consistent with our study statistics. Dashraath et al.[10, 17] attributed fetal growth restriction to prolonged respiratory insufficiency, which increased maternal hypoxia, promoted the release of potent vasoconstrictors such as endothelin-1 and hypoxia-inducible factor, and led to hypoperfusion of the placenta and reduced oxygen supply to the fetus. Consequently, whether the surgical indications for caesarean section in COVID-19-positive pregnant women should be moderately relaxed, such as through stricter monitoring of maternal and fetal vital signs during labour, to reduce the potential increased risk of fetal distress posed by the novel coronavirus, warrants consideration.

In addition, as this study matched gestational age as a covariate in the PSM analysis, the gestational week among cases was balanced at baseline. This resulted in a lack of analytical results on preterm birth rates, despite it being an important indicator in many studies on the impact of COVID-19 on pregnant women[18, 19]. Some authors believe that the causes of preterm birth are multifactorial. The presence of symptoms such as fever, cough, and nausea may affect the physical and psychological conditions of COVID-19-infected pregnant women to varying degrees, potentially increasing the rate of premature birth. Healthcare-related factors also play a key role. Medical judgement may be influenced by whether the patient is infected with COVID-19. Consequently, more proactive measures, such as caesarean section, might be taken for COVID-19-positive pregnant women to mitigate potential risks to the mother and foetus. Thus, the increasing rate of premature birth cannot be solely attributed to the risk posed by COVID-19 infection itself.

Our study also found that women in the positive group exhibited lower satisfaction with caesarean section anesthesia and poorer postoperative recovery. This may be explained by the significant influence of physical discomfort and emotional anxiety associated with COVID-19 infection. Symptoms such as fever, fatigue, and cough, along with emotional distress and concerns about the health of both the mother and foetus, contribute to an increased physiological and psychological burden on pregnant women. Perioperative maternal patients are already a high-risk population for anxiety and depression[20]. Recent reports have shown that COVID-19 may result in acute changes in behaviour, cognition, personality, or consciousness, including anxiety disorders and depression, which could exacerbate pre-existing mental illnesses or lead to post-traumatic stress disorder[21–23]. It is therefore imperative to identify the psychological impact of COVID-19 infection on pregnant women. This requires close monitoring of the emotional changes in pregnant women with COVID-19 during clinical diagnosis and treatment, timely provision of psychological counselling, and patient explanations of clinical decisions and disease progression. These measures can reduce the likelihood of perioperative anxiety and depression in pregnant women with COVID-19 and increase patient satisfaction. However, whether the novel coronavirus can induce heightened sensitivity to pain stimuli, diminish anesthetic efficacy, or impact postpartum recovery in pregnant women should be explored through further scientific research.

Our study has several limitations. Firstly, this is a retrospective cohort study with a small sample size from a single center, and propensity score matching caused some sample size loss. We used the inverse probability of treatment weighting method to mitigate this loss. However, routine nucleic acid testing for pregnant women ceased after 2023 due to local policy changes in China, preventing the inclusion of more subjects. Secondly, we did not collect data on the vaccination status of each subject. Studies have shown that COVID-19 infection poses significant risks to pregnant women and fetuses, but vaccination during pregnancy is safe. Therefore, vaccination status may also affect our study results. Thirdly, we only collected neonatal outcomes for one month after the caesarean section, necessitating further research and long-term follow-up. Lastly, we did not classify the severity of COVID-19 in positive pregnant women, as they could not undergo chest radiography or other imaging examinations.

Overall, our findings hold certain implications for combating the novel coronavirus, which may persist in human populations in the long term. our study demonstrates that the incidence of neonatal distress syndrome is higher in neonates born to COVID-19-infected mothers compared to non-infected mothers. However, there were no significant differences between the two groups in terms of other clinical outcomes, such as preeclampsia, stillbirth, neonatal mortality, and maternal mortality. Although our sample size is small, our results suggest that active measures, such as caesarean sections, should be taken to avoid a higher risk of neonatal foetal distress. This may have some reference value for a potential resurgence of the epidemic in the future.

COVID-19 infection combined with related clinical symptoms, could increase the likelihood of fetal distress and reduce maternal satisfaction with anaesthesia and postoperative recovery quality scores.

Competing interests: The authors declare no competing interests.

Funding statement: This study is supported by funding from the Beien Anesthesia Research Project supported by Bethune Charitable Foundation (BNMR-2021004). The funders have no role in the study design, data collection and analysis, decision to publish, or manuscript preparation. Compensation to those who suffer harm from trial participation will be payed from the funding according to the severity of the adverse event.

Author Contributions: JM conceived the primary idea of the study. All authors contributed to the writing of the manuscript. FY and JW drafted this paper in close cooperation with JM. ZL collected and managed the study data. The study was supervised by RH and JM. Data analysis was performed by JW. All authors read and approved the final manuscript.

Patient Consent Form: Not applicable.

Patient and public involvement: Patients and/or the public were not involved in the design, conduct, reporting, or dissemination plans of this research.

Data Sharing Statement: The datasets generated and/or analysed during the current study are available upon reasonable request.

Acknowledgements: I would like to thank Professor Anxin Wang for providing guidance on statistical methods, Professor Wanli Gao and her team for patient management and perioperative medical treatment.

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No competing interests reported.

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The impact of coronavirus disease 2019 (COVID-19) on the perioperative outcomes of emergency cesarean section in maternal and neonatal prognosis: A propensity score-matched analysis

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Background

Methods

Study Design and Data Source

Patient Population

Baseline Characteristics

Outcomes

Statistical Analysis

Ethics Approval

Results

Discussion

Conclusion

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References

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