Double Jeopardy: The Intersection of COVID-19 and Pregnancy in an Educational Hospital, Northern Iran, Gorgan

Document Type : Original Articles

Authors

1 Infectious Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

2 Department of Obstetrics and Gynecology, Golestan University of Medical Sciences, Golestan, Iran

3 Department of Microbiology, Faculty of Medicine, Golestan University of Medical Sciences, Gorgan, Iran.

4 Nursing Research Center, Golestan University of Medical Sciences, Gorgan, Iran.

5 Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.

10.32592/ARI.2025.80.3.629

Abstract

With the onset of the severe acute respiratory syndrome coronavirus-2 pandemic, there were controversial theories regarding the potential consequences of the virus on pregnant women and delivery outcomes. During the past three years, a great diversity of literature reported various data regarding covid-infected mothers and pregnancy-related complications including preterm birth, stillbirth, preeclampsia, cesarean delivery, etc., however; the exact influences which can be exerted by the virus and possibility of vertical transmission, still remained obscure. Here we described the clinical features and outcomes of delivery in 16 laboratory confirmed COVID-19-infected mothers referring to a hospital in northern Iran from August 2020 to December 2021. Clinical records, laboratory results, and chest CT scans in addition to such samples as maternal peripheral blood, umbilical cord blood, placental blood, vaginal secretion, placental tissue, breast milk after first lactation, and neonatal throat swab and peripheral blood were collected to answer the questions raised on the possibility of vertical transmission of COVID-19 and transferring maternal immunity to the neonates, all the aforementioned specimen were evaluated based on molecular and serological assays. SARS-CoV-2 RNA was not detected in vaginal secretions and placental tissue. SARS-CoV-2 IgG and IgM antibodies were detected in 15 and 4 maternal blood samples, respectively; in one breast milk sample (IgM), two umbilical cord blood (IgG) samples, two placental blood (IgG) and two neonatal blood (IgG) samples. Chest CT scan of abnormal cases revealed typical signs of viral pneumonia. According to the current study there seems to be associations between SARS-CoV-2 infection and the risk of preterm birth; however, no intrauterine vertical transmission of SARS-CoV-2 was found. These results also suggest the possibility of passive IgG transfer from the infected mothers to their neonates.

Keywords

1. Introduction

SARS-CoV-2, the virus responsible for COVID-19, has notable effects on pregnant women. According to several studies ( 1 ), the consequences of SARS-CoV-2 infection during pregnancy can be significant. These consequences may include to an increased risk of complications, such as preterm birth, preeclampsia, and severe respiratory issues in expectant mothers. Additionally, research has shown the potential for vertical transmission, whereby the virus can be passed from the mother to the fetus, although this is relatively rare. Therefore, it is crucial for pregnant women to take precautions and follow recommended guidelines to minimize the risk of exposure to the virus and its potential adverse effects on both their health and that of their unborn child ( 2 ).Certain viral respiratory outbreaks, including SARS-CoV, MERS, and 2009 Influenza A (H1N1), have been known to induce detrimental effects on pregnancy. These negative impacts include an increased higher risk of adverse outcomes such as preterm birth, stillbirth, maternal mortality, severe respiratory distress, pneumonia, acute respiratory distress syndrome (ARDS), and complications affecting both maternal and fetal health ( 3 , 4 ). Over the past five years, literature has reported various data on complications in pregnancies of - mothers infected with COVID-19, including preterm birth (PTB), stillbirth, preeclampsia, cesarean delivery. However, the exact pathogenesis, including possibility of vertical transmission, remains obscure ( 5 ). Another question is whether maternal SARS-CoV-2 antibodies transfer to the fetus or neonate before birth or during lactation. Furthermore, there aren’t proved explanations of exact clinical characteristics of COVID-19 in both the mother and her neonate ( 6 ). Here we described the clinical features and pregnancy outcomes in 16 mothers with laboratory- confirmed COVID-19-infection who referred to a hospital in northern Iran from August 2020 to November 2021.

2. Materials and Methods

2.1. Study Population and Clinical Samples

The population of interest for the current study consisted of pregnant women with laboratory-confirmed cases of COVID-19 who referred to the maternity ward of Sayyad Hospital in Northern Iran for delivery. The women were recruited from August 2020 to November 2021.

2.2. Data collection

The study's included pregnant women with a laboratory-confirmed diagnosis of COVID-19 at any point during pregnancy. Exclusion criteria included non-pregnancy and a negative COVID-19 test. Immediately after admission and birth, respectively, sterile Dacron swabs with flexible plastic shafts were used to collect maternal and neonatal throat and nasopharyngeal, which were tested for SARS-CoV-2 using the Iranian Center for Disease Control and Prevention (CDC) recommended Kit (PISHTAZ TEB COVID-19 One-Step RT-PCR Kit Dual-target gene (nucleocapsid protein (N) and RNA-dependent RNA polymerase (RdRp)) following WHO guidelines for qRT-PCR. All samples were processed simultaneously at the Department of Microbiologyat the School of Medicine atGorgan University of Medical Sciences inGorgan, Iran. Maternal peripheral blood samples were collected, and sera were separated by centrifugation. SARS-CoV-2 IgG and IgM antibodies were assessed in the sera using IDEAL TASHKHIS IgG and IgM ELISA kits. Umbilical cord blood, placental blood, vaginal secretions, placental tissue, neonatal throat swabs, and peripheral blood samples were collected immediately after delivery in an isolated negative-pressure operating room. Additionally, breast milk samples from patients with COVID-19 were collected after their first lactation. All aforementioned specimens were tested using qRT-PCR and serological assays. The clinical records and chest CT scans of all patients were meticulously examined to extract relevant data.

3. Results

3.1. Clinical Features of Mothers with COVID-19 Infection

From August 2020 to November 2021, 16 third-trimester pregnant women were hospitalized as part of a 16-month study.Their clinical and laboratory data, as well as treatments, are summarized in Table 1. Ten of the women underwent caesarean sections, and six vaginal deliveries. The patients' ages ranged from 21 to 38 years old, and their gestational ages at delivery were between 26 weeks and 4 days and 38 weeks and 5 days. BMI ≥ 30 kg/m2 was reported in 7 cases. No underlying diseases were detected except for one with cardiovascular disease.7 patients developed gestational diabetes, while only one had preeclampsia. Ten out of the 16 patients reportedfever before or during delivery, with body temperatures ranging from 36.5°C to 38.0°C. Two patients experienced postpartum feverwith temperatures ranging from 37°C to 39°C. Other symptoms of upper respiratory tract infection were also reported: eleven patients had a cough, seven reported myalgia, and sore throat and chest pain was observed in two and three women, respectively. Seven women indicated dyspnea, and two reported headaches.  Gastrointestinal symptoms were not observed in any of the patients. None exhibited gastrointestinal symptoms, required mechanical ventilation or died from pneumonia caused by COVID-19. Three patients were admitted to the ICU, and six and five patients used nasal cannula and nonrebreather mask for oxygen support, respectively. Nine patients received antiviral therapy (table 1). Clinical parameters, such as lymphopenia (<1.0 × 109 cells per L) and elevated C-reactive protein levels (>10 mg/L), were extracted from medical records (Table 2). Elevated concentrations of alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) were reported in five cases, and increased white cell counts (>11.0 × 109/L) were observed in four patients. Table 2 summarizes the results of the SARS-CoV-2 qRT-RNA and anti-SARS-CoV-2 antibody ELISAs for 16 patients . All COVID-positive tests were confirmed by nasopharyngeal and oropharyngeal qRT-PCR. SARS-CoV-2 RNA was not detected in vaginal secretions or placental tissue. Serological tests performed on mothers' blood (15 IgG positive and 4 IgM positive), breast milk (one IgM positive), umbilical cord blood (two IgG positive) and placental blood (two IgG positive) (Table 2). We performed chest CT scans on all 16 patientsbut we only accessed 8 scans. In abnormal cases,the scans showed typical signs of viral pneumonia, such as decreased diffuse and bilateral ground-glass opacities, patchy lung consolidation, blurred borders, and lesions that merged into strips (Figure 1).

Clinical characteristics Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Sample 7 Sample 8 Sample 9 Sample 10 Sample 11 Sample 12 Sample 13 Sample 14 Sample 15 Sample 16 n (%)
Date of admission 25-Jan 24-Dec 19-Feb 26-Oct 23-Feb 22-Mar 5-Jun 22-Nov 11-Nov 3-Jan 22-Dec 21-Dec 22-Oct 22-Jun 23-Jun 21-Apr ..
Age (years) 34 32 21 27 32 23 32 32 28 36 22 25 27 34 38 22 ..
Obesity BMI ≥ 30 kg/m2 No Yes No No No No Yes No Yes Yes Yes No Yes Yes No No 7 (43.75)
Smoking No No No No No No No No No No No No No No No No 0
Nulliparous No Yes Yes Yes No Yes No No Yes Yes Yes No No No No Yes 8 (50)
Gestational age at delivery 37W & 5D 26W & 4D 35W & 3D 38W & 5D 30W & 1D 34W & 4D 37W & 6D 37W 37W & 4D 34W 35W & 2D 33W & 2D 38W & 3D 33 W 34W & 3D 27W & 4D ..
Preterm delivery No Yes Yes No Yes Yes No No No Yes Yes Yes No Yes Yes Yes 10 (62.5)
Comorbidities No No No No No No No CVD No No No No No No No No 1 (6.25)
Preeclampsia No No No No Yes No No No No No No No No No No No 1 (6.25)
Gestational diabetes No Yes Yes No No Yes No No No Yes No No Yes Yes Yes No 7 (43.75)
Anaemia Yes No No No No No No No Yes No No No No No No No 2 (12.5)
Asthma No No No No No No No No No No No No No No No No 0
Signs and symptoms
Fever Yes No Yes Yes No Yes Yes No Yes No No Yes Yes No Yes Yes 10 (62.5)
Cough Yes No No Yes Yes Yes Yes No No Yes Yes No Yes Yes Yes Yes 11 (68.75)
Myalgia Yes No Yes Yes No No Yes No No No No No Yes Yes Yes No 7 (43.75)
Sore throat No No No No No No Yes No No Yes No No No No No No 2 (12.5)
Chest pain No Yes No No No No No Yes No No No No No No No Yes 3 (18.75)
Fatigue No No No No No No No No No No No No No No No No 0
Dyspnea No No No Yes No Yes Yes Yes No No No No No Yes Yes Yes 7 (43.75)
Diarrhea No No No No No No No No No No No No No No No No 0
Headache Yes No No No No No No No No No No No Yes No No No 2 (12.5)
Postpartum fever No No No Yes No No No No Yes No No No No No No No 2 (12.5)
Laboratory characteristics
White-cell count (× 109/L) 10 15.2 8.7 7.9 8.6 12 7.8 9.8 11.7 10.4 7.6 10.5 8.9 10.4 12.6 8.5 ..
Low or normal leukocyte count(<9·5 × 109 cells per L) No No Yes Yes Yes No Yes No No No Yes No Yes No No Yes 7 (43.75)
Lymphocytes count(× 109/L) 1.5 0.6 1.74 1.58 1.72 0.96 2.17 2.54 1.75 1.04 2.28 2.73 1.24 1.64 2.14 1.36 ..
Lymphopenia (<109 cells per L) No Yes No No No Yes No No No No No No No No No No 2 (12.5)
C-reactive protein Pos Pos Pos Pos Pos Neg Pos Neg Neg Neg Neg Posi Posi Pos Pos Pos 11 (62.5)
D-dimer (μg/mL) .. .. .. .. .. 3.35 .. 6.18 .. .. .. .. .. 2.16 2.49 .. ..
S.G.P.T (ALT) (U/L) 26 16 .. 14 36 55 15 30 .. 13 15 20 11 18 68 12 ..
S.G.O.T (AST) (U/L) 30 67 .. 25 39 74 27 95 .. 28 19 27 21 26 146 42 ..
Elevated ALT (>45 U/L) or AST (>35 U/L) No Yes .. No No Yes No Yes .. No No No No No Yes Yes 5 (31.25)
Sodium (mEq/L) 137 138 .. 139 137 143 142 141 139 .. 139 136 135 133 150 136 ..
Potassium (mEq/L) 3.8 4.1 .. 3.9 3.9 4.2 4.5 4.5 4.8 .. 3.8 4.1 4.2 4.1 4.3 4.2 ..
CT evidence of pneumonia
Typical signs of viral infection Yes .. .. Yes No Yes Yes Yes No .. .. No No Yes Yes Yes 8 (50)
Type of delivery
Method of delivery C-section C-section Vaginal Vaginal C-section Vaginal C-section Vaginal C-section Vaginal Vaginal C-section C-section C-section C-section C-section ..
Indication for C-section Meconial Fetal Distress .. .. Severe preeclampsia .. Rep2 .. Leiomyomas .. .. Pretermlabor COVID-19 pneumonia Pretermlabor COVID-19 pneumonia Preterm labor, meconial ..
Treatment after delivery
Oxygen support (nasal cannula) No No No No No No Yes Yes Yes No No Yes Yes Yes No No 6 (37.5)
Oxygen support (nonrebreather mask) No Yes No Yes No Yes No No No No No No No No Yes Yes 5 (31.25)
Mechanical ventilation No No No No No No No No No No No No No No No No 0
Maternal ICU admission No No No No No Yes No No No No No No No No Yes Yes 3 (18.75)
Antiviral therapy No No Yes Yes Yes Yes Yes Yes No No No No No Yes Yes Yes 9 (56.25)
Use of corticosteroid No No No No No No No No No No No No No No No No 0
CVD: Cardiovascular Disease, W: Weeks, D: Days
 Table 1.The clinical and laboratory characteristics, and treatments of pregnant women.
Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Sample 7 Sample 8 Sample 9 Sample 10 Sample 11 Sample 12 Sample 13 Sample 14 Sample 15 Sample 16 n (%)
Viral RNA detection
RT-PCR SARSCOV2 Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos Pos 16 (100)
Vaginal secretions Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
Placenta tissues Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
Anti SARS-CoV-2 Ab
IgG in Blood samples Pos Pos Neg Pos Pos Pos Pos Pos Pos Neg Neg Neg Pos Pos Pos Pos 12 (75)
IgM in Blood samples Neg Pos Pos Neg Neg Neg Neg Neg Neg Neg Pos Neg Neg Neg Neg Pos 4 (25)
IgG in Milk samples Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
IgM in Milk samples Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Pos Neg Neg Neg Neg Neg 1 (6.25)
IgG in Umbilical cord blood Pos Neg Neg Neg Neg Neg Neg Pos Neg Neg Neg Neg Neg Neg Neg Neg 2 (12.5)
IgM in umbilical cord blood Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
IgG in Placental blood Pos Neg Neg Neg Neg Neg Neg Pos Neg Neg Neg Neg Neg Neg Neg Neg 2 (12.5)
IgM in Placental blood Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
Neg: Negative, Pos: Positive
 Table 2.Maternal SARS-CoV-2 serological and molecular outcomes.

Figure 1. Chest CT scan (transverse plane) of seven patients.

3.2. Clinical Characteristics of Neonates Born To Mothers With COVID-19 Infection

The infants were delivered in an isolated room and immediately separated from their mothers. Ten of the infants were born full-term,and six were premature. There were a total of 16 live births, with two fatal distress cases. Three newborns passed away after delivery. Eight infants had a birth weight of less than 2500g, three of them did not survive. Apgar scores were recorded for 13 newborns at 8-10, 1-, and 5-min. Three neonates who ultimately died had Apgar scores of 5-6 and 7-8, 1-, and 5-min. Pneumonia and pneumothorax were observed in seven and three newborns, respectively. Four neonates required mechanical ventilation, and nine required oxygen therapy. Two newborns had Respiratory Distress Syndrome (RDS), one had intraventricular hemorrhage (IVH), and six had sepsis. According to CDC recommended qRT-PCR test, SARS-CoV-2 nucleic acid was not observed in any cases. Furthermore, Anti SARS-CoV-2 IgG was detected in blood samples of two newborns (Table 3).

Neonate 1 Neonate 2 Neonate 3 Neonate 4 Neonate 5 Neonate 6 Neonate 7 Neonate 8 Neonate 9 Neonate 10 Neonate 11 Neonate 12 Neonate 13 Neonate 14 Neonate 15 Neonate 16 n (%)
Clinical Data
Birth weight (grams) 3300 900 2800 2650 1300 2250 2500 3020 3050 2250 1845 1650 3700 1970 2200 800 ..
Low birth weight (<2500 g) No Yes No No Yes No No No No Yes Yes Yes No Yes Yes Yes 8 (50)
Preterm delivery No Yes Yes No Yes Yes No No No Yes Yes Yes No Yes Yes Yes 10 (62.5)
Apgar score (1 min, 5 min) 9, 10 5, 7 9, 10 9, 10 6, 8 7, 9 9, 10 8, 9 9, 9 9, 9 8, 9 8, 9 7, 9 8, 9 8, 9 5, 7 ..
Meconial Yes No No No No No No Yes No No No No No No No Yes 3 (18.75)
Mechanical ventilation No Yes No No Yes No No No No No No No No Yes No Yes 4 (25)
Oxygen therapy No Yes No No Yes Yes No No No Yes No Yes Yes Yes Yes Yes 9 (56.25)
Pneumothorax No Yes No No Yes No No No No No No No No Yes No No 3 (18.75)
Pneumonia No No No No Yes No No No No Yes No Yes Yes Yes Yes Yes 7 (43.75)
RDS No Yes No No No No No No No No No No No Yes No No 2 (12.5)
IVH No No No No No No No No No No No No No No No Yes 1 (6.25)
Sepsis No No No No Yes No No No No Yes No Yes Yes Yes No Yes 6 (37.5)
NEC No No No No No No No No No No No No No No No No 0
Fetal distress No Yes No No No No No No No No No No No No No Yes 2 (12.5)
Neonatal Death No Yes No No Yes No No No No No No No No No No Yes 3 (18.75)
Viral RNA & Antibody
SARS-CoV-2 nucleic acid Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
Anti SARS-CoV-2 IgG Pos Neg Neg Neg Neg Neg Neg Pos Neg Neg Neg Neg Neg Neg Neg Neg 2 (12.5)
Anti SARS-CoV-2 IgM Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg Neg 0
Table 3.Neonatal outcomes.

4. Discussion

Pregnancy triggers physiological adjustments that ensure optimal fetal development and delivery outcomes. However, these adjustments also make mothers more susceptible to pathogens. The potential for neonatal morbidity and developmental malformations resulting from viral infections during pregnancy underscores the importance of understanding the likelihood of vertical SARS-CoV-2 transmission ( 4 ). In this study, none of the newborns' nasopharyngeal swabs tested positive for the virus. Additionally, the molecular tests of umbilical cord blood, placental blood, vaginal secretions, placental tissue, and neonatal peripheral blood were negative, which is consistent with the previous studies ( 7 ). While some studies suggest evidence of vertical transmission of SARS-CoV-2through positive neonatal throat swab tests, which may indicate  postnatal transmission, data showing SARS-CoV-2 RNA in placenta, amniotic fluid, and umbilical cord blood support the hypothesis of vertical transmission, albeit rare ( 8 ).

The expression of angiotensin-converting enzyme 2 (ACE2), transmembrane protease serine 2 (TMPRSS2), dipeptidyl peptidase 4 (CD26), and CD147 in syncytiotrophoblast (SCT), villous (VCT), and extra villous (ECT) cytotrophoblast, as well as gynecological organs like the vagina and ovary, which are involved in viral entry, may explain these results. However, the findings in the literature are controversial ( 9 ). The study analyzed the clinical characteristics of SARS-CoV-2 infected mothers and their newborns. The results revealed that fever, cough, myalgia, dyspnea, sore throat, and gastrointestinal symptoms were common among participants. These findings aligns with other studies and show that these symptoms are not unique to SARS-CoV-2 infected pregnant women ( 10 ). A literature review revealed mixed results on the link between COVID-19 and preeclampsia (PE). Some studies found an association between the two factors ( 11 ), while others did not. It is important to note that these studies referred to a temporary condition called preeclampsia-like syndrome (PE-like syndrome), which shares symptoms with PE and makes it difficult to distinguish between the two conditions ( 12 ). Our research also did not uncover any associations between COVID-19 and PE. The survey then examined the relationship between COVID-19 and obesity. Apart from the Center for Disease Control and Prevention (CDC), which identified obese individuals as a high-risk group for severe illness and death from SARS-CoV-2, previous research has also found links between this condition during pregnancy and adverse outcomes from various infections, including CMV, documented influenza pandemics, Varicella Zoster, malaria, Listeria monocytogenes, and SARS. This correlation can be attributed to leptin, an adipocyte-derived hormone that plays a role in food intake, reproduction, and immune-metabolism. Leptin is linked to inflammatory pathways that can exacerbate COVID-19. Consistent with the literature, this research found that 43.75% of mothers with BMI ≥ 30 kg/m2 ( 13 ). Our study revealed maternal-fetal immunity, which occurs in two phases. The first phase occurs before birth through the transfer of maternal antibody to the fetus.The second phase occurs after birth during lactation. Our most significant finding was the discovery of maternal-fetal immunity. This occurs in two stages: before birth,when antibodies are transfered from the mother to the fetus, and after birth, during lactation period ( 14 ). Of the maternal plasma samples tested, 25% were positive for SARS-CoV-2-specific IgM and 75% for IgG. These results are similar to those of Fenizia et al., who found 32% IgM and 63% IgG in maternal plasma ( 15 ). Additionally, two mothers tested negative for both IgG and IgM, indicating an early stage of infection. IgG crosses the placenta passively during late pregnancy, while IgM cannot due to its macromolecular structure ( 16 ). We detected SARS-CoV-2-specific IgG in both placental and umbilical cord blood of two newbornswhose mothers had SARS-CoV-2-specific IgG. The newborns tested positive for SARS-CoV-2 RNA, did not require ventilation orany specific medication. These findings align with those of other studies that have found maternal IgG in cord blood and placenta ( 17 ). However, vaccination should also be considered. Jones et al. reported a case of a vaccinated mother with positive antibodies against SARS-CoV-2 in umbilical cord blood ( 18 ). Additionally, some studies suggest that the absence of antibodies in cord blood may be due to timing of infection or decline in placental antibody concentration during the second or third trimester of pregnancy ( 17 ). Analysis of serological data revealed the presence of IgM in the breastmilk of a mother who tested positive for IgM and negative for IgG. Previous studies have suggested that breastmilk, with its components such as SIgA (90%) and SIgM (8-15%), IgG (2-5%), and cytokines, provides newborns with protection against infections for up to six months after birth. ( 19 ).

Our results differ from those of some studies that detected IgG and SIgA in breastmilk ( 20 ), but are consistent with other studies ( 21 ). one possible explanation for these results is that milk IgG originates from serum, and only 11.8% of SARS-CoV-2 IgG was detected in blood samples one week after infection.It takes about three months for the concentration to reach its peak (100%) ( 22 ). Further follow-up of this mother could help investigate the presence of other antibodies in her breastmilk. Like most investigations,our study did not find SARS-CoV-2 RNA in mothers' milk. These data contradict the findings of a few studies that claim the SARS-CoV-2 transmission through breastmilk , although none of these studies attempted to culture the SARS-CoV-2 isolates  from positive milks to assess their infectivity ( 23 ). Given the limited research on the breastmilk of COVID-infected mothers, it is recommended that mothers take hygienic precautions, such as wearing facemasks, washing their hands, and disinfecting surfaces, during the lactation period.

The authors of this study aimed to investigate the connection between SARS-CoV-2 and gestational complications. They built on previous research that warned of detrimental effects of the viral family on pregnancy outcomes, such as preterm birth (PTB), fetal growth restriction (FGR), low birth weight (LBW), preterm labor, and stillbirth. The study found PTB, CS, LBW, and neonatal death rates of 62.5%, 62.5%, 50%, and 18.75%, respectively. These rates are comparable to those reported in review articles, which showed varying rates of PTB (14.3% - 61.2%) and neonatal death (0-11.7%), as well as an increasing trend of CS and LBW in mothers with COVID-19 ( 24 ). Pregnancy is associated with several physiological, immunological, and hormonal changes that increase susceptibility to respiratory infections.

The immune system suppression commonly experienced during pregnancy can contribute to infection progression. Placental hypoxia can result in cytokine storms, which can damage the placenta and cause fetal growth restriction, preterm birth, or abortion. Moreover, inflammatory factors prompt endothelial dysfunction, which is a hallmark of PE, as well as end-organ damage, fetal hypoxemia and ultimately ,fetal distress ( 25 ). One limitation of the current study is the small sample size. Furthermore, it is regrettable that the research did not include women in their first and second trimesters of pregnancy. The study also failed to investigate the potential damage thar SARS-CoV-2 could cause to the placenta, which could provide valuable data on the relationship between SARS-CoV-2 and pregnancy complications. Lastly, the lack of an appropriate ELISA kit prevented the study from examining SIgM and SIgA levels in breast milk. The primary goal of this study was to assess the potential for vertical transmission of SARS-CoV-2 and its effects on pregnancy outcomes. Our findings did not show evidence of vertical transmission, they revealed that pregnant women infected with SARS-CoV-2 were at risk of preterm birth, low birth weight, and cesarean delivery. Despite the limited sample size, this study provides valuable insights into the impact of SARS-CoV-2 on pregnancy. Further research is needed to fully understand the mechanisms and effects of SARS-CoV-2 on pregnancy and to develop strategies to prevent or reduce adverse maternal and neonatal outcomes.

Acknowledgment

The authors would like to thank the staff at Sayyad hospital, the laboratory staff, and the Department of Microbiology atGolestan University of Medical Sciences in Gorgan, Iran, for the technical support.

Authors' Contribution

Conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript: AT, SDH.

Designed the data collection instruments, coordinated and supervised data collection: AT, SDH, ZS, EK, PC, MY, MB.

Collected data: SDH, MB, MY, MR, MH.

Collected and reviewed the radiological images: MB.

Carried out the initial analysis: AT, SDH, MH, PC, MR.

All authors approved the final manuscript as submitted and agreed to be accountable for all aspects of the work.

Ethics

Our study of pregnant women with laboratory-confirmed COVID-19 adhered to ethical guidelines. We ensured transparency and respect for participants' autonomy. We initiated the informed consent process by providing clear and comprehensible information and detailed written consent forms that outlined the purpose, procedures, and confidentiality of the study. Patients were given ample time to review and ask questions, and we emphasized the voluntary nature of their involvement. This ethical framework was maintained throughout the study period, with ongoing communication channels to address any inquiries or concerns. Our goal was to protect the rights and well-being of the pregnant women involved in our research.

Conflict of Interest

The authors declare that they have no conflict of interest related to this study.

Funding statement

The Ethics Committee of Golestan University of Medical Sciences granted ethical approval for data and specimen collection (Ethics code: IR.Goums.REC.1399.176).

Data Availability

All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.

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Archives of Razi Institute
Volume 80, Issue 3
May and June 2025
Pages 629-637

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