Abstract
Introduction
COVID-19 infection in pregnancy ranges from asymptomatic infection to severe disease. However, the maternal and pregnancy outcomes are primarily favorable. Acute Respiratory Illness (ARI) score is a Visual Triage Checklist for Acute Respiratory symptoms created by the ministry of health of Saudi Arabia 12 to screen the patient for acute respiratory infection with MERS-CoV. It has been used during the COVID-19 pandemic to identify suspected cases and place patients in isolation precautions if the score is≥ 4.
Method
This study is a cross-sectional study of all pregnant women who tested positive for COVID-19 in four medical centers located in four different cities in Saudi Arabia. The study period was from 1/3/2020 until 31/10/2020. Outcomes investigated were the prevalence of COVID infection in pregnant women at the time of delivery. Rate of asymptomatic disease, different maternal and pregnancy outcomes. Women were divided into symptomatic and asymptomatic groups according to the ARI score. The two groups were compared in maternal, perinatal, and neonatal outcomes. Furthermore, the cohort was divided according to maternal age into two groups: women of advanced maternal age ≥ 35 years and younger. The two groups were compared in maternal, perinatal, and neonatal outcomes
Results
During the study period, 9573 women gave birth at KAMCs, and 402 pregnant women were identified as COVID positive. Out of all COVID-positive women, only 394 women gave birth at KAMCs. The screening for COVID infection differed between the centers, but the testing was the same by the Nasopharyngeal polymerase chain reaction (PCR) swab. In Riyadh, screening was based on ARI scoring at the beginning of the pandemic. Then, it became universal. In Jeddah, the screening was based on ARI scoring. Any woman who scored four or more was labeled as suspected, and she was tested. Finally, in Madinah and Dammam, the screening was universal throughout the study.
The prevalence of COVID-19 infection among women who gave birth at KAMCs was 4.2% (402/9573). (CI 3.8–4.6%). At the time of diagnosis, most women (62%) were asymptomatic. The most common symptoms were cough and shortness of breath. Twenty-two women (5.5%) had Pneumonia, and five women (1.3%) needed admission to Intensive care units (ICU). One woman died due to respiratory failure.
When pregnancy outcomes were compared between symptomatic and asymptomatic women, pregnancy in symptomatic women was more likely to be complicated by Abortion (6 versus 2% p-value 0.00), fetal death (3 versus 1.3%), and cesarean delivery (30.8 versus 22.4%, p-value 0.001). COVID-positive pregnant women of advanced maternal age (AMA) were more likely to be symptomatic, have Abortion (5 versus 1%, p-value 0.01), and have Preterm delivery (17 versus 11% p-value 0.01) than younger women. In addition, neonatal death was more common in AMA COVID-positive women than younger (4 versus 0%), regardless of COVID-related symptoms.
Conclusion
Most of the COVID-infected pregnant women are asymptomatic. Therefore, the ARI scoring system does not help to triage patients. Symptomatic women, especially those older than 35, tend to have a higher maternal and pregnancy complication rate.
Keywords: COVID-19, Pregnancy, Acute respiratory infection score, ARI score, Advanced maternal age maternal death
Introduction
SARS-CoV-2 is the strain of coronavirus causes COVID-19. In December 2019, a cluster of cases of Pneumonia due to COVID-19 was identified in Wuhan, China [1]. On March 12, 2020, the world health organization (WHO) defined the outbreak as a pandemic [2]. By the end of March. 2022, there were more than 490,00,000 reported cases of COVID and more than 6,000,000 deaths worldwide [3]. In Saudi Arabia, there have been 750,000 reported cases and 9039 related deaths.
Pregnant women are less likely to acquire the infection than the general population [4].
COVID-19 infection in pregnancy ranges from asymptomatic infection to mild disease (no evidence of Pneumonia or hypoxia) to moderate disease (viral Pneumonia) until severe disease (severe pneumonia, e.g., with SpO2 below 90% on room air) and critical illness (acute respiratory Distress Syndrome, sepsis, septic shock, or complications such pulmonary embolism or acute coronary syndrome) [5]. Most pregnant women infected with SARS-CoV-2 are asymptomatic [6]. Most symptomatic women experience only mild or moderate cold/flu-like symptoms [7]. Maternal mortality is rare; the estimated SARS-CoV-2 associated maternal mortality rate is 2.4 per 100 000 (95% CI 1.3–4.0) [8].
The severe illness appears to be more common in later pregnancy. 83% of symptomatic women were diagnosed at or beyond 28 weeks, with 52% diagnosed at or beyond 37 weeks [9]. Pregnant women had higher odds of Pneumonia (OR 1.99, 95% CI 1.81–2.19) [10], admission to intensive care (OR 2.13, 95% CI 1.53–2.95), and requirement of invasive ventilation (OR 2.95, 95% CI 2.28–2.94) [6] and higher odds of death (OR 1.84, 95% CI 1.30–2.61) [10]. The maternal risk factors associated with severe COVID-19 are age 35 years and older, OR 1.83 (95% CI 1.27–2.63); BMI 30 kg/m2 and above, OR 2.37 (95% CI 1.83–3.07); for chronic hypertension, OR 2.0 (95% CI 1.14–3.48); and for pre-existing diabetes, OR 2.12 (95% CI 1.62–2.78) [6]. Maternal COVID-19 is also associated with an increased cesarean delivery (CD) rate. The rate of CD was 49% in women with symptomatic COVID-19 and 29% for a historical control group before the COVID-19 pandemic [9].
The overall outcomes for babies born to women with COVID-19 were favorable, with over 95% born in good condition [6]. When COVID-19 infected pregnant women were compared to non-infected pregnant women, there was an increased risk of low birth weight (OR 1.89 95% CI 1.14–3.12) [11] and stillbirth (OR 2.84, 95% CI 1.25–6.45) [6].
In Saudi Arabia, The first positive COVID-19 case was confirmed in March 2020, with more cases sporadically appearing in the following weeks [3]. COVID vaccine became available in Dec 2020 and became a requirement to enter the workplace in Aug 2021. Acute Respiratory Illness (ARI) score is a Visual Triage Checklist for Acute Respiratory symptoms ( Fig. 1). It was created by the ministry of health of Saudi Arabia [12] to screen the patient for acute respiratory infection with MERS-CoV and identify suspected cases and place them in isolation precautions if the score is≥ 4 [13]. It has been used during the COVID-19 pandemic. MOH recommended patient isolation if the score was≥ 6. In KAMC, the cut-off of 4 has been used to screen patients and label people with ARI scores equal to or more than four as suspects.
Fig. 1.
Visual triage checklist for acute respiratory illness (ARI score). 13
This study aimed to compare pregnancy outcomes between symptomatic and asymptomatic COVID-19 infected pregnant women before vaccination was available.
Method
This study is a cross-sectional study of all pregnant women who tested positive for COVID19 in four King Abdulaziz medical centers (KAMC) in the ministry of national guard health affairs (MNGHA) located in 4 different cities, Saudi Arabia. Riyadh, Jeddah, Madinah and Dammam. The study period is from 1/3/2020 until 31/10/2020.
The primary outcome is to calculate the prevalence of COVID-19 infection among pregnant women tested in KAMC. The secondary outcomes are to study the maternal characteristics of COVID-positive pregnant women delivered at KAMCs and their pregnancy outcomes, including maternal, fetal, and neonatal outcomes.
Maternal characteristics include age, Body mass index (BMI), Gravidity, parity, the ARI score at presentation, and past medical history. The maternal outcomes are symptoms upon presentation, rate of the asymptomatic carrier, maternal disease diagnosed during pregnancy, therapy required, admission to intensive care unit (ICU), respiratory support, cesarean delivery(CD), and postpartum complications. Secondary outcomes also included fetal outcomes such as Abortion, intrauterine fetal death after 20-week gestation, and preterm delivery before 37-week gestation. Preterm rupture of membrane before 37-week gestation and Neonatal outcomes such as gestational age at the time of delivery, birth weight, and disease diagnosed before discharge. The cohort was divided into symptomatic and asymptomatic groups according to the ARI score. Symptomatic women who had an ARI score of 4 or more. A comparison was made between the two groups in maternal, fetal, and neonatal outcomes. Furthermore, the cohort was divided into women of Advanced maternal age ≥ 35 years and younger group. The two groups were compared in different maternal and pregnancy outcomes.
Statistical analysis
Numerical variables were reported as means and medians, while categorical variables were reported as percentages. Association between ARI scores among Covid positive pregnant women and Maternal and fetal outcomes were tested using Chi-square and Fisher’s exact test. In addition, the association between maternal age among Covid positive pregnant women and Maternal and fetal outcomes was tested using Chi-square and Fisher’s exact test.
Results
During the study period, 402 pregnant women were identified as COVID positive during the study period in four KAMC centers, Riyadh, Jeddah, Madinah, and Dammam. Analysis was done on 394 women. 8 women were excluded from analysis because they delivered outside those facilities. ( Fig. 2). The prevalence of COVID-19 infection among women presented to KAMC facilities was 4.2%. (CI 3.8–4.6%). The prevalence varied slightly between the cities—the prevalence was in Riyadh at 5%, Jeddah at 3.8%, Madinah and Dammam at 2.4%.
Fig. 2.
Study`s patient population.
Baseline Maternal characteristics: ( Table 1).
Table 1.
Baseline characteristic.
| Characteristic | Number (%) | Confidence interval (CI) or Interquartile range (IQR) |
|---|---|---|
| Maternal Age in years at Time of Delivery (mean) | 30.8 | CI 0.6 |
| BMI (mean) | 30.57 | CI 0.6 |
| Gravida (Median) | 3 | IQR 2 |
| Para (median) | 2 | IQR 2 |
| Gestational age at diagnosis (median) | 38 | IQR 6 |
| Medical disease diagnosed before pregnancy | 96 (24) | |
|
20 (5) | |
|
7 (1.8) | |
|
6 (1.5) | |
|
6 (1.5) | |
|
3 (0.8) | |
|
2 (0.5) | |
|
2 (0.5) | |
|
1 (0.3) | |
|
1 (0.3) | |
|
5 (1.3) |
The mean maternal age was 30.8 years; the mean BMI was 30.6. median gestational age at the time of diagnosis was 38 weeks. Three hundred eighty-five women carried a singleton, eight twins, and one triplet. Most women were healthy. Only 24% had a positive past medical history. The most common past medical disorder was Endocrine disorder (Diabetes mellitus & hypothyroidism).
Maternal outcome ( Table 2).
Table 2.
Maternal outcome.
| Acute Respiratory Infection (ARI) Score upon Presentation (median) | 0 (IQR 4) |
| Asymptomatic (ARI score less than 4) | 248 (62%) |
| Symptomatic (ARI score 4 or more) | 146 (38%) |
| ARI Score 0 | 223 (56%) |
| COVID related symptoms upon presentation | Frequency (%) |
|
39 (9.7) |
|
29 (7.2) |
|
28 (7) |
|
19 (4.7) |
|
15 (3.7) |
|
13 (3.2) |
|
13 (3.2) |
|
10 (2.5) |
|
7 (1.7) |
|
4 (1.3) |
| Admission to hospital | 329 (83) |
| Pneumonia | 22 (5.5) |
| Maternal disease diagnosed during pregnancy | 89 (23) |
|
7 (2) |
|
3 (1) |
|
1 (0.3) |
|
1 (0.3) |
|
2 (0.5) |
|
53 (13) |
|
8 (2) |
|
5 (1.3) |
| Therapy | |
| Any Therapy | 63 (16) |
|
22 (5.6) |
|
5 (1.3) |
|
35 (9) |
|
17 (4) |
| Respiratory support | |
| Intensive care unit (ICU) admission and Respiratory support | 5 (1.2) |
| Extracorporeal Membrane Oxygenation (ECMO) | 2 (0.5) |
| Maternal Death | 1 (0.3) |
At the time of diagnosis, most women (62%) were asymptomatic. The majority of women (55%) had an ARI score of 0. The most common COVID-related symptoms were cough, shortness of breath, and fever. The cohort was divided into two groups Asymptomatic with an ARI score of less than 4 (146 women) and symptomatic with a higher ARI score (248 women).
Most women were admitted to hospital (83%) either because of pregnancy or COVID-related symptoms. Twenty-two women (5.5%) were diagnosed with Pneumonia based on symptoms and positive radiological findings. Only 15% of all women required some treatment. The most common treatment given was antibiotics (5.5%). In addition, five women (1.3%) needed ICU admission, and two women required extracorporeal membrane oxygenation (ECMO). One woman died in ICU due to respiratory failure. She was 23 years old, previously healthy, and She had spontaneous twin gestation. During her second trimester, she presented with respiratory symptoms and was diagnosed with COVID. She was transferred to KAMC-J ICU intubated in respiratory failure.
Pregnancy outcome: ( Table 3).
Table 3.
Pregnancy outcome.
| Singleton | 385 |
| Twins | 8 |
| Triplet | 1 |
| Gestational Age at time of delivery (median) | 39 (IQR 3) |
| Abortion (%) | 13/393 (3.5) |
| Stillbirth (%) | 7 /354 (2) |
| Preterm delivery | 47/354 (13) |
| Preterm premature rupture of membrane | 4/354 (1.3) |
| Fetal complication (hydrops, anomalies, abnormal amniotic fluid growth restriction) | 16/378 (4.2) |
| Cesarean delivery (CD) | 102 (25%) |
| Indication for CD (%) | |
|
27(27) |
|
27(27) |
|
6 (6) |
|
10(10) |
|
3 (3) |
|
1 (1) |
|
1 (1) |
|
5 (5) |
|
22 (21) |
Among women identified with COVID in pregnancy, 13 women had a miscarriage. Seven (2%) pregnancies were complicated by Intrauterine fetal death. Preterm delivery before 37 weeks occurred in 47 women (13%). The median gestational age at the time of delivery was 39 weeks. The rate of CD was 24%. Elective repeat CD and Abnormal fetal monitoring were the most common indications for CD. (26% each).
Neonatal outcome ( Table 4).
Table 4.
Neonatal outcome.
| Disease | Cases (%) | |
|---|---|---|
| Neonatal death | 4 (1) | |
| low birth weight | 20 (5) | |
| Jaundice | 61 (15.2) | |
| Respiratory | 17 (4.2) | |
| Genito-urinary | 14 (3.5) | |
| Cardiac | 11 (2.7) | |
| Musculo-skeletal | 5 (1.2) | |
| Gastrointestinal | 3 (0.7) | |
| Multiple anomalies | 3 (0.7) | |
| Skin | 2 (0.5) | |
| others | Inborn error of metabolism | 1 (0.2) |
| Hypoxic ischemic encephalopathy | 1 | |
| Multiple disease | 16 (4) | |
All neonates were admitted to the neonatal intensive care unit to ensure proper isolation of newborns. Breastfeeding was not allowed. 20 (5%) newborns had Low birth weight. Four neonates died in the neonatal period due to prematurity complications. All mothers of Neonatal deaths (NND) were older than 35 years of age and had COVID-related symptoms. The most common neonatal disease was neonatal jaundice (15%). Other neonatal outcomes such as birth weight and neonatal complications were similar in both groups. None of the neonates had COVID positive testing by throat swab.
Comparing symptomatic to asymptomatic women
Maternal characteristics ( Table 5).
Table 5.
Comparing maternal characteristics between symptomatic to Asymptomatic women.
| Variable | Symptomatic N = 146 (%) |
Asymptomatic N = 248 (%) |
P value | |
|---|---|---|---|---|
| Maternal age at time of delivery (Mean) | 31.02 | 30.67 | ||
| Advanced maternal age | 65 (45) | 83 (33) | 0.024 | |
| Body mass index | 29 | 31 | 0.001 | |
| Gravidity | 3.77 | 3.45 | ||
| Therapy required | 44 | 18 | 0.001 | |
| Respiratory support | 5 | 0 | 0.019 | |
| Gestational age at time of delivery (Mean) | 37.45 | 38.12 | SD 4 | |
| Past medical history | Respiratory disease | 1 | 1 | |
| Hematological disease | 1 | 6 (3) | ||
| Thyroid disease | 3 (2) | 0 | ||
| Cardiac disease | 1 | 0 | ||
| Diabetes mellitus | 0 | 2 | ||
| Thrombophilia | 1 | 0 | ||
Age, parity, and Gravidity were almost the same, but symptomatic women were more likely to be of advanced maternal age (45 versus 33%).
Maternal complication ( Table 6).
Table 6.
Comparing maternal and pregnancy outcome between symptomatic to Asymptomatic women.
| Outcome | Symptomatic N=146 (5) | Asymptomatic N= 248 (%) | p-value | |
|---|---|---|---|---|
| Pneumonia | 22 | 0 | 0.001 | |
| Intensive care unit admission | 5 (3.4) | 0 | 0.01 | |
| Perinatal complication | ||||
| Any perinatal complication | 57(40) | 85(35) | 0.262 | |
| Gestational Diabetes | 25(17) | 26(11) | ||
| Hypertensive disease in pregnancy | 4 (3) | 1 | ||
| Preeclampsia | 3 (2) | 1 (0.4) | ||
| Postpartum complication | ||||
| Any postpartum complication | 12 (9) | 20 (8) | 0.848 | |
| Postpartum hemorrhage | 4 (3) | 12 (5) | ||
| Worsening of respiratory status | 1 (1) | 0 | ||
| Wound infection | 2 (2) | 1 (0.4) | ||
| Fever | 2 (2) | 3 (1) | ||
| Anal sphincter tear | 0 | 1 (0.4) | ||
| Anemia | 0 | 2 (1) | ||
Symptomatic women were more likely to require treatment and respiratory support and were diagnosed with Pneumonia in 22 (5.5%), five patients (1%) were admitted to ICU, and one patient died.
Pregnancy outcome ( Table 7).
Table 7.
Comparing perinatal outcomes between symptomatic to Asymptomatic women.
| Outcome | Symptomatic 146 (%) | Asymptomatic 248 (%) | p-value | |
|---|---|---|---|---|
| Abortion | 8 (6) | 5 (2.1) | 0.001 | |
| Fetal death | 4 (3) | 3 (1.3) | 0.001 | |
| Preterm delivery | 27 (11) | 20(15) | 0.4 | |
| PPROM | 1 (1) | 3 (1) | 0.4 | |
| Low birth weight | 6 (4) | 14 (6) | 0.4 | |
| Fetal complications (hydrops, anomalies and IUGR) | 4 (3) | 12 (5) | 0.4 | |
| Cesarean delivery | 45(31) | 55(22) | 0.001 | |
| Indication for CS | Repeat | 12 (8) | 24 (10) | 0.104 |
| Abnormal CTG | 16 (11) | 10 (4) | ||
| Failure to progress | 4 (3) | 2 (1) | ||
| Twins | 2 | 1 | ||
| Maternal request | 0 | 1 | ||
| Failed operative delivery | 1 (1) | 0 | ||
| Malpresentation | 2 (1) | 3 (1) | ||
| Other indications | 9(6) | 13 (5) | ||
Symptomatic women had a higher rate of Abortion (6 versus 2% p-value of 0.001) and fetal death (3 versus 1.3%) than symptomatic women. Prenatal complications were more common among symptomatic than asymptomatic women (28.5% versus 20%). Gestational diabetes (GDM) was the most common complication (17.5 versus 11.6) among asymptomatic women. Symptomatic women were more likely to have CD at 30.8% versus 22.4% (p-value 0.001).
Neonatal outcome: ( Table 8).
Table 8.
Comparing Neonatal outcomes between Symptomatic to Asymptomatic women.
| Symptomatic N = 146 (%) | Asymptomatic N = 248 (%) | ||
|---|---|---|---|
| Any Neonatal Complication | 50 (34) | 87 (35) | 0.650 |
| Neonatal death | 2 (1.4) | 2 (0.8) | 0.6 |
| Birth weight (gm) | 2935 | 2625 | 0.001 |
Neonatal death was higher in the symptomatic group 4/146 (3%). All NND occurred in women with AMA.
Comparing COVID positive women of Advanced Maternal Age to younger women ( Table 9).
Table 9.
Comparing COVID positive women with advanced maternal age (AMA) to younger women.
| AMA N = 120 | Non-AMA N = 274 | P value | |
|---|---|---|---|
| Age (mean) | 38 | 27 | |
| BMI (mean) | 32.5 | 30 | 0.001 |
| Gravidity (median) | 5 (IQR 1) | 2 (IQR 2) | 0.001 |
| Parity (median) | 3 (IQR3) | 1 (IQR 2) | 0.001 |
| ARI score at presentation (median) | 2 (IQR4) | 0 (IQR4) | 0.03 |
| Abortion | 6 (5.2) | 3 (1.1) | 0.01 |
| GA at delivery (mean in weeks) | 36.6 (SD6) | 38.4 (SD3.7) | 0.001 |
| Preterm delivery before 37 weeks | 20 (17) | 29 (11) | 0.01 |
| Cesarean delivery | 36 (33%) | 65 (24%) | 0.115 |
| Birth weight in gm (median) | 3030 (IQR 710) | 3000 (IQR 640) | 0.3 |
| Neonatal death | 4 | 0 |
Women with advanced maternal age were more likely to have higher BMI, Gravidity, and parity. In addition, they were more likely to be symptomatic. Pregnant women younger than 35 years had lower median ARI scores (0 versus 0, p-value of 0.03) than older women. AMA women had a higher rate of Abortion (5 versus 1%, p-value 0.01), Preterm delivery (17 versus 11% p-value 0.01), and lower mean gestational age at delivery (36 versus 38.4 weeks) when compared to younger women. Neonatal death was more common in AMA than in the younger group (4 versus 0%). There was no difference between women of AMA and younger women in the mode of delivery or birth weight.
Discussion
Maternal symptoms
Most of the COVID-19 positive women (56%) were asymptomatic at diagnosis. This finding is similar to data from London and New York centers, where all pregnant women admitted to birthing units had routine swabs for polymerase chain reaction (PCR) testing for COVID-19. It was found that 88% of the women who tested positive were asymptomatic [14], [15],. The most common COVID-related symptoms were cough, shortness of breath, and fever, like the finding of a systematic review of 24 studies, including a total of 324 pregnant women who tested positive for COVID [16].
In the UKOSS study [9], COVID-19 infection appears to be more common in later pregnancy. Most women were hospitalized in the third trimester or peripartum (bearing in mind that Admission at term to give birth will contribute to this distribution). Symptomatic COVID-19 was principally diagnosed in the third trimester: 83% of symptomatic women were diagnosed At or beyond 28 weeks, 52% were diagnosed at or beyond 37 weeks.
Acute respiratory infection scoring system
Using the ARI scoring system did not help triage patients. 62% of patients had an ARI score of less than 4, which is the cut-off for recommended isolation by MOH. This study could not calculate the sensitivity or specificity because it did not include non- COVID women. Mimish et al. [17]. tested the sensitivity and specificity of the ARI scoring system in MERS-CoV cases. A cut of 4 had a sensitivity of 74% and a specificity of 19%. The sensitivity and specificity of the scoring system did not improve even with giving more weight to the history of exposure to positive cases over the last two weeks. Jazieh et al. [18]. investigated the yield of using the ARI scoring system as a screening tool for COVID-19 infection in cancer patients. The positive predictive value was only 18.24%, with a confidence interval (CI) of 0 − 32 with fluctuating results parallel to the prevalence of the disease and a negative predictive value of 96 (86–99%).
Maternal hospital admission
In this study, most women were admitted (83%). The reason for admission was the policy of admitting all pregnant at the beginning of the pandemic or COVID-related symptoms later in the pandemic. In the UKOSS study [9], admitting asymptomatic women were principally to give birth (68%). For symptomatic women, the reasons for admission were symptomatic COVID-19, giving birth, and other reasons.
Maternal pneumonia
Seventy women needed a chest x-ray (CXR), and only 30% had abnormal findings. The maternal disease was mainly mild. Only 2% required respiratory support, and one had mortality. Five women in this cohort were admitted to ICU with one mortality. In a meta-analysis of studies including 753 women pregnancies of COVID-positive women, 78 women (10%) were admitted to ICU. Among the 1100 pregnant women, five cases of maternal death were reported [19].
Abortion
Pregnancy loss before 20 weeks occurred in 3.4% of cases. It was statistically more common in symptomatic women (6 versus 2%) and more common in women with AMA 5.2 versus 1.2%. Seasonal influenza has been associated with higher rates of miscarriage [20]. The relationship between influenza and birth rates during the 1918 pandemic in the United States, Denmark, Sweden, and Norway was investigated by examining monthly birth rates from 1911 through 1930. Birth rates declined in study populations in spring 1919 by a mean of 2.2 births per 1000 persons, representing a 5 –15% drop below baseline levels (P < 0.05). The 1919 birth rate reached its trough 6.1–6.8 months after the Autumn pandemic peak, suggesting that missing births were attributable to excess first trimester miscarriages in ∼1 in 10 women who were pregnant during the height of the pandemic. Pandemic-related mortality was insufficient to explain observed patterns [21].
Preterm labor before 37 weeks
Preterm delivery before 37 weeks occurred in 13% of this study group. Women with COVID infection and AMA had a statistically significant higher rate of preterm delivery when compared to younger women (17 versus 11%). The pooled proportion of preterm birth< 37 weeks was 41% (CI) 25–57 in a systematic review, and a meta-analysis of 6 studies included 32 COVID-positive pregnant women [22]. In India, the overall proportion of babies born preterm (i.e., before 37 weeks gestation) increased from 8·3% in the pre-lockdown period to 10·4% in the post-lockdown period [23]. Regardless of the status of documented COVID infection. Similar findings were also reported in Nepal [24].
Most of the preterm labor in the Indian study [25] was spontaneous. The rate of spontoons preterm delivery increased from 63% in the pre-lockdown cohort to 67% in the lockdown cohort. By contrast, the proportion of iatrogenic preterm births decreased from 13% in the pre-lockdown cohort to 7% in the lockdown cohort. This reduction is most likely due to the number of antenatal visits pre-lockdown compared with post-lockdown, which might have led to a decrease in the identification of pregnancies requiring medically indicated preterm birth, resulting in a decreased rate of iatrogenic preterm births [25].
Cesarean delivery
CD rate was 24% in this study population. This rate is l1% lower than the rate reported in the same institution before the pandemic [26]. Cesarean delivery was more common in symptomatic women (31 versus 22%). CD in India during the COVID-19 lockdown period was 37%, significantly higher than the rate during the pre-lockdown period of 33·0% (p = 0·04) [25]. The rate of CD was 91% in a Meta-analysis of 6 studies that included 41 positive women. The most common indication for CD in this cohort was an elective repeat CD and abnormal fetal monitoring.
Intrauterine fetal death
The rate of IUFD in the study population was 2%, and it was more common among symptomatic women (3 versus 1.3%). This rate is similar to the rate reported in India.
2.2–3.2% [25] and Nepal [24] 1.4 − 2% during the pandemic. The IUFD rate during the study period was much higher than the reported rate of 3.42/1000 in Riyadh, Saudi Arabia, before the pandemic n 2017 [27].
The UK Obstetric Surveillance System reported a stillbirth rate of 12.1 per 1000 births in women with confirmed coronavirus disease COVID-19 versus the national rate of 4–5 per 1000 [28].
During the COVID pandemic, the stillbirth rate increased regardless of whether the pregnant women were diagnosed with COVID infection. In a study done by Khalil et al. [l], the stillbirth rate was compared between 1681 birth in the pre-pandemic period and 1718 birth in the pandemic period, the overall incidence of stillbirth was significantly higher during the pandemic period (9.31 per 1000 births); none associated with COVID-19; than during the pre-pandemic period (2.38 per 1000 births) the difference, 6.93 per 100 birth [95% CI, 1.83–12.0]; P = 0.01 [29].
Neonatal complication
NND occurred in 4 cases (1%) of 394. This rate is similar to the rate reported, during the pandemic, in Saudi Arabia at 3/288 [30], China at 2/155 [16], and Italy at 3/444 [19].
COVID-19 vaccination
This study was done before the availability of the COVID vaccine. More than 347 150 women in the UK and USA have had a COVID-19 vaccine during pregnancy with no concerning safety signals. There is excellent evidence of vaccine efficacy with 98% of women admitted to hospital and getting severe infections have not had the vaccine [31] A recent meta-analysis evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0.85; 95% CI 0.73–0·99). There was no evidence of a higher risk of adverse outcomes, including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum hemorrhage, maternal death, intensive care unit admission, lower birth weight, or neonatal intensive care unit admission [32].
Conclusion
Most of COVID infected pregnant women were asymptomatic. Therefore, the ARI scoring system did not help triaging patients. Symptomatic women older than 35 tend to have a higher maternal and pregnancy complication rate.
Funding
None.
Ethical approval
The research was approved by Ethical board of king Abdulaziz international research center.
Contribution statement
Taghreed Shams owns the research idea, supervised data collection and wrote the manuscript. Hashem Alhashemi did the data cleaning and analysis. All other authors contributed to data collection.
Conflict of interest
None.
Acknowledgements
None.
Data availability
Data is available upon request.
References
- 1.Li Q., Guan X., Wu P., Wang X., Zhou L., Tong Y., Ren R., Leung K.S.M., Lau E.H.Y., Wong J.Y., Xing X., Xiang N., Wu Y., Li C., Chen Q., Li D., Liu T., Zhao J., Liu M., Tu W., Chen C., Jin L., Yang R., Wang Q., Zhou S., Wang R., Liu H., Luo Y., Liu Y., Shao G., Li H., Tao Z., Yang Y., Deng Z., Liu B., Ma Z., Zhang Y., Shi G., Lam T.T.Y., Wu J.T., Gao G.F., Cowling B.J., Yang B., Leung G.M., Feng Z. Early transmission dynamics in Wuhan, China, of novel coronavirus-infected pneumonia. N Engl J Med. 2020;382:1199–1207. doi: 10.1056/NEJMoa2001316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.WHO WHO/Europe. Coronavirus disease (COVID-19) outbreak - WHO announces COVID-19 outbreak a pandemic (Online). 〈https://www.euro.who.int/en/health-topics/health-emergencies/coronavirus-covid-19/news/news/2020/3/who-announces-covid-19-outbreak-a-pandemic〉 [8 November 2020].
- 3.Ministry of health Saudi daily report Sept 25, 2021.
- 4.Docherty A.B., Harrison E.M., Green C.A., Hardwick H.E., Pius R., Norman L., et al. Features of 20 133 UK patients in hospital with covid-19 using the ISARIC WHO Clinical Characterisation Protocol: prospective observational cohort study. BMJ. 2020;369:m1985. doi: 10.1136/bmj.m1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Coronavirus (COVID-19) infection and pregnancy green top guidelines. Royal College of Obstetricians and Gynaecologists. Version 14: updated 25 August 2021.
- 6.Allotey J., Stallings E., Bonet M., Yap M., Chatterjee S., Kew T., et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis. BMJ. 2020;370:m3320. doi: 10.1136/bmj.m3320. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Public Health England. COVID-19: investigation and initial clinical management of possible cases. 2020; Website.
- 8.Knight M., Bunch K. National Perinatal Epidemiology Unit, University of Oxford; Oxford: 2021. MBRRACE-UK: saving lives, improving mothers’ care. Rapid report 2021: learning from SARS-CoV-2-related and associated maternal deaths in the UK June 2020-March 2021. (Website) [Google Scholar]
- 9.Vousden N., Bunch K., Morris E., Simpson N., Gale C., O’Brien P., et al. The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: a national cohort study using the UK Obstetric Surveillance System (UKOSS) PLoS One. 2021;16(5) doi: 10.1371/journal.pone.0251123. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Martinez-Portilla R.J., Sotiriadis A., Chatzakis C., Torres-Torres J., Espino Y., Sosa S., et al. Pregnant women with SARS-CoV-2 infection are at higher risk of death and pneumonia: propensity score matched analysis of a nationwide prospective cohort (COV19Mx) Ultrasound Obstet Gynecol. 2021;57(2):224–231. doi: 10.1002/uog.23575. [DOI] [PubMed] [Google Scholar]
- 11.Wei S.Q., Bilodeau-Bertrand M., Liu S., Auger N. The impact of COVID-19 on pregnancy outcomes: a systematic review and meta- analysis. CMAJ. 2021;193(16):E540–E548. doi: 10.1503/cmaj.202604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.The new COVID-19 guidance document [ Saudi Center for Disease prevention and Control. Novel Corona Virus (2019-nCoV) Infection Guidelines V1.0. Kingdom of Saudi Arabia: Saudi Center for Disease Prevention and Control Ministry of Health; 2020] produced by Saudi CDC provides HCFs with a new visual triage (VT)
- 13.Command and Control Center Ministry of Health Kingdom of Saudi Arabia Scientific Advisory Board. Infection prevention and control guidelines for the Middle East respiratory syndrome coronavirus (MERS-CoV) infection. 4th ed. 2017.
- 14.Khalil A., Hill R., Ladhani S., Pattisson K., O’Brien P. SARS-CoV-2 in pregnancy: symptomatic pregnant women are only the tip of the iceberg. Am J Obstet Gynecol. 2020;0 doi: 10.1016/j.ajog.2020.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Sutton D., Fuchs K., D’Alton M., Goffman D. Universal screening for SARS-CoV-2 in women admitted for delivery. N Engl J Med. 2020;382:2163–2164. doi: 10.1056/NEJMc2009316. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Juan J., Gil M.M., Rong Z., Zhang Y., Yang H., Poon L.C. Effect of coronavirus disease 2019 (COVID-19) on maternal, perinatal and neonatal outcome: systematic review. Ultrasound Obstet Gynecol. 2020;56(1):15–27. doi: 10.1002/uog.22088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Alfaraj SH, Al-Tawfiq JA, Gautret P, Alenazi MG, Asiri AY, Memish ZA. Evaluation of visual triage for screening of Middle East respiratory syndrome coronavirus patients. New Microbes and New Infections, Volume 26 Number C, November 2018. [DOI] [PMC free article] [PubMed]
- 18.Jazieh A.R., Alghamdi M., Alkaiyat M., Al Johani S.M., Damlaj M. A retrospective evaluation of the value of COVID-19 screening and testing in patients with cancer: aiming at a moving target. J Infect Public Health. 2021;14(7):949–953. doi: 10.1016/j.jiph.2021.05.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Di Toro F., Gjoka M., Di Lorenzo G., De Santo D., De Seta F., Maso G., et al. Impact of COVID-19 on maternal and neonatal outcomes: a systematic review and meta-analysis. Clin Microbiol Infect. 2021;27(1):36–46. doi: 10.1016/j.cmi.2020.10.007. Epub 2020 Nov 2. PMID: 33148440; PMCID: PMC7605748. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Dorélien A. The effects of in utero exposure to influenza on birth and infant outcomes in the US. Popul Dev Rev. 2019;45:489–523. doi: 10.1111/padr.12232). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Bloom‐Feshbach K, Lone S, C´ecile V, Kåre M, Miller Mark A, Magnus G, Viggo A. Natality decline and miscarriages associated with the 1918 influenza pandemic: the Scandinavian and United States experiences. J Infect Dis 2011;204(8):1157–64. [DOI] [PMC free article] [PubMed]
- 22.Di Mascio D., Khalil A., Saccone G., Rizzo G., Buca D., Liberati M., Vecchiet J., Nappi L., Scambia G., Berghella V., D'Antonio F. Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis. Am J Obstet Gynecol MFM. 2020;2(2) doi: 10.1016/j.ajogmf.2020.100107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Choudhary R., Kumari V. COVID-19 and preterm birth - authors’ reply. Lancet Glob Health. 2021;9(2) doi: 10.1016/S2214-109X(20)30458-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Kc A., Gurung R., Kinney M.V., et al. Effect of the COVID-19 pandemic response on intrapartum care, stillbirth, and neonatal mortality outcomes in Nepal: a prospective observational study. Lancet Glob Health. 2020;8(10):e1273–e1281. doi: 10.1016/S2214-109X(20)30345-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 25.Kumari V., Mehta K., Choudhary R. COVID-19 outbreak and decreased hospitalisation of pregnant women in labour. Lancet Glob Health. 2020;8(9):e1116–e1117. doi: 10.1016/S2214-109X(20)30319-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Shams T., Gazzaz T., Althobiti K., Alghamdi N., Bamarouf W., Almarhoumi L., et al. Comparison of pregnancy outcomes between women of advanced maternal age (≥35 years) versus younger women in a tertiary care center in Saudi Arabia. Ann Saudi Med. 2021;41(5):274–279. doi: 10.5144/0256-4947.2021.274. Epub 2021 Oct 7. PMID: 34618607; PMCID: PMC8497009. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 27.Rahman SU, Abdulghani MH, Faleh KA, Khalil M, Mustafa MM, Anabrees J, Mansour MY, Mirza A, Mousafeiris K, Mubarak M, Kamal M. Perinatal mortality in Saudi Arabia: profile from a private setup. J Clin Neonatol 2020;9:8–12.
- 28.Knight M., Bunch K., Vousden N., et al. UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Group. Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population-based cohort study. BMJ. 2020;369:m2107. doi: 10.1136/bmj.m2107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Khalil A., von Dadelszen P., Draycott T., Ugwumadu A., O’Brien P., Magee L. Change in the incidence of stillbirth and preterm delivery during the COVID-19 pandemic [published online ahead of print, 2020 Jul 10] JAMA. 2020;324(7):705–706. doi: 10.1001/jama.2020.12746. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Al-Matary A., Almatari F., Al-Matary M., AlDhaefi A., Alqahtani M.H.S., Alhulaimi E.A., et al. Clinical outcomes of maternal and neonate with COVID-19 infection - multicenter study in Saudi Arabia. J Infect Public Health. 2021;14(6):702–708. doi: 10.1016/j.jiph.2021.03.013. Epub 2021 Apr 20. PMID: 34020209; PMCID: PMC8056848. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Royal collage of physician and surgeons. Coronavirus (COVID-19) Infection in Pregnancy. Information for healthcare professionals Version 15: Published Monday 7 March 2022.
- 32.Prasad S., Kalafat E., Blakeway H., et al. Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy. Nat Commun. 2022;13:2414. doi: 10.1038/s41467-022-30052-w. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Data is available upon request.