Iranian Society of Gynecology Oncology

Document Type : Review Article


1 Vali-E-Asr Reproductive Health Research Center, Family Health Research Institute, Tehran University of Medical Sciences, Tehran, Iran

2 Department of Perinatology, Vali-E-Asr Hospital, Tehran University of Medical Sciences, Tehran, Iran

3 Department of Neonatology, Yas Women Hospital, Tehran University of Medical Sciences, Tehran, Iran

4 Blood Transfusion Organization, Mazandaran, Iran


Several studies have described multisystem inflammatory syndrome (MIS) in children, but very few investigations presented this syndrome among neonates (MIS-N). The present study has reviewed the current knowledge about MIS-N, its etiology, symptoms, and outcomes to attract special attention with an eye on earlier diagnosis and treatment of newborns affected by perinatal SARS-CoV-2-infection. A narrative review study was conducted (Tehran, Iran, 2021). All types of full English articles (up to October 1 2021) were included. Detailed research on academic search engines was performed. The implemented Mesh-based keywords were "SARS-COVID-2" OR "COVID-19" OR "coronavirus" AND "Neonate" OR "Neonatal" OR "Newborn" AND "Multisystem Inflammatory Syndrome" OR "MIS-N" OR "inflammatory response syndrome" AND "Pregnancy" OR "Perinatal" OR "prenatal". Finally, 15 Full-text articles were included that met the eligibility criteria. Available data related to the disease, its etiology, presentations, and its outcome were collected and discussed. The cause of MIS-N is the transmission or production of SARS-CoV2 antibodies in response to SARS-CoV2 infection. By involving different organs, the clinical manifestations of MIS-N may mimic sepsis, toxic shock syndrome, RDS, Kawasaki disease, necrotizing enterocolitis, myocarditis, meningitis/encephalitis, aortic thrombosis, ETC. Besides the clinical presentations, detecting reactive anti-SARS-CoV-2 IgG antibodies could be a notable clue in MIS-N diagnosis. Supportive therapy, suppressing the autoimmune and inflammatory responses, anti-platelet agents, and anticoagulants were reported as effective therapeutic agents to improve the outcome. The present study highlighted the possibility of MIS-N as an infrequent but severe syndrome consequent to perinatal COVID-19 infection. Although the diagnosis is still controversial, clinical suspicion, laboratory findings, and early treatment initiation could improve the outcome of this immunological disease.


Main Subjects


Today, vertical transmission of SARS-CoV-2 is well identified (1, 2). Intrauterine transplacental transmission, Intrapartum secretions exposure, postnatal exposure to infected patients, and breastfeeding transmission are potential mechanisms for neonatal SARS CoV-2 infection (3). These perinatal transmissions are responsible for possible impairments of fetal health, resulting in severe neonatal morbidity and mortality (4, 5). Besides neonatal demise, respiratory, nervous, and immune system complications are reported as the adverse effects related to neonatal SARS-CoV-2 infection (6).
Recently, few investigations showed that fetal inflammatory response syndrome secondary to maternal SARS-CoV-2 infection might be responsible for the immune system's overreaction and excessive production of pro/anti-inflammatory and immuno-regulatory/modulatory cells. This overresponse of the immune system causes the release of a large amount of interferon resulting in cytokine storm and neonatal multisystem inflammatory syndrome (MIS-N) (7-9).
MIS-N following perinatal SARS-CoV-2 infection as a new and rare condition has been reported by very few studies. In this life-threatening condition, different body organs (heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal may become inflamed (10). The signs and symptoms associated with MIS-N include severe fever, cardiovascular and pulmonary complications, nausea, vomiting, diarrhea, inflammatory bowel disease, neck pain, bloodshot eyes, headache, and mucocutaneous symptoms (like Kawasaki disease) (3, 11). IgM and IgG antibodies against SARS-CoV-2 were also shown in more than 80% of cases with MIS (10, 11).
To prevent MIS-related adverse events, conducting further studies are worthy. Although several studies have described MIS in children, very few investigations presented this syndrome among neonates. Herein, this study reviewed the current knowledge about MIS-N, its etiology, signs, and symptoms to attract special attention with an eye on earlier diagnosis and treatment of newborns affected by perinatal SARS-CoV-2-infection.



A narrative review study was conducted in the Maternal, Fetal, and Neonatal Research Center, affiliated with Tehran University of Medical Sciences, Tehran, Iran, in 2021.
All types of full English articles, including case reports, case series, pilot studies, letters to the editor, and original, systematic, and meta-analysis review studies (up to October 1, 2021) were included. Detailed research was performed on academic search engines (Cochrane Library, ISI of Web Science, Scopus, PubMed, and Google Scholar databases). The implemented Mesh-based keywords for the study were considered as "SARS-COVID-2" OR "COVID-19" OR "coronavirus" AND "Neonate" OR "Neonatal" OR "Newborn" AND "Multisystem Inflammatory Syndrome" OR "MIS-N" OR "inflammatory response syndrome" AND "Pregnancy" OR "Perinatal" OR "prenatal". Moreover, a few relevant studies were added through reviewing the reference lists. After reviewing the abstracts, irrelevant or duplicate research was excluded. All studies related to children or pediatric multisystem inflammatory syndrome (MIS-C) were also exited. The primary outcome was gathering available data related to the disease, its etiology, presentations, and its outcome.


Results and Discussion
Through a computerized search, 43 studies were yielded. After exclusion of duplicate references (9), irrelevant studies without pointing to the subject (2), studies related to Children, Pediatric, or Infant Multisystem Inflammatory Syndrome (12), and lack of information (3), finally, 15 Full-text articles were included that met the eligibility criteria (Figure 1).
  Figure 1. Flow chart of the included studies
 Figure 1. Flow chart of the included studies
After reviewing included studies, a data extraction list was designed to gather information regarding the author's name, country, publication date, study design, as well as neonate's age, sex, disease manifestations, laboratory findings, medical treatments, and neonatal outcomes. Table 1 summarizes the information of included studies. Based on the findings extracted from studies, the results are categorized as follows:

Table 1. List of information (author's name, country, publication date, study design, neonate's age, sex, disease manifestations, laboratory findings, medical treatments, and neonatal outcomes) related to included articles

Outcome; Deat/ Discharge Treatment Serology, laboratory & Echo findings Clinical presentations Maternal
COVID- 19 RT PCR & antibody
n (male/female, age at
Presentation (day), preterm/term
Authors' name, country, publication date, study design  
anticonvulsant, immunoglobulin, methylprednisolone, aspirin
+ve IgG
-ve RT PCR
Fever, tachycardia, tachypnea, moderate subcostal and intercostal retraction, rhonchi -ve* RT PCR
+ ve** IgG
1(male),10days, term
Amulya et al., (22), 2021 Sep 27, Letter to the Editor  
Normal Blood count, septic screen, metabolites, and renal function, elevated LDH, CKMB, troponin T, and CPK  
Echo: Coronary artery dilatation of LAD and
Oxygentherapy, antibiotics, IV immuneglobulin + ve IgG
+ veRT PCR
Afebrile,respiratory distress, feed intolerance, abdominal
distention, dehydrated, tachypneic , shock, lethargic, bilious discharge, dilated bowel loops,, bowel wall edema, Stage 111A
necrotizing enterocolitis
+ve RT PCR 1(male), 1 day, preterm:34 weeks) Thakuretal., (20), India, September 24, 2021, Case Report  
metabolic acidosis ,hyponatremia,neutropenia,thrombocytopenea, elevated BUN, CRP, procalcitonin, deranged Prothrombin time international normalized
ratio, positive Stool occult blood,protein urea
2/18 Oxygen therapy, ventilation and respiratory support,
Cardiac support, Antibiotics, Steroids, IVIG, Aspirin, Surfactant
+ve IgG =19
+ve IgM=1
+ve RT PCR=0
Encephalopathy, refusal of feeds,
Lethargy, Fever, Seizure, Hypoglycaemia, Vomiting, Cardiac murmur, Tachycardia, Ascites, Excessive
crying, Right
+ve IgG =9 cases
+ve IgM=4 cases
+ve RT PCR=9 cases
20 (16/4), 1-30 days, 4/16 More et al., (13) India, September 7, 2021, Case series  
Leukocytopenia, Leucocytosis,ElevatedDdimer, TropT, PROBNP,
LDH, CRP,Procalcitonin, Ferritin, Thrombocytopenia,Thrombocytosis, Deranged
coagulation profile
Echo : LV
Dysfunction, Biventricular
Dysfunction, pericardial
Effusion, Prominent
Right limb amputation, discharged Corticosteroids, heparin, recombinant tissue plasminogen activator, surgical embolectomy followed by right limb amputation +ve IgG
+ve IgM
-ve RT-PCR
Blackish discoloration of the toes of feet + ve IgG
+ ve IgM
- ve RT-PCR
1,(N/A), 6 days, term Amonkar et al., (23) India,  2021 September 5, case report  
Elevated CRP, ESR, ITL6, procalcitonin, ferritin, LDH, N-terminal pro-brain natriuretic peptide, D-dimer  
Discharged Antibiotics, Ventilation and respiratory support, remdesivir, Levetiracetam, phenobarbitone, Dexamethasone, methylprednisolone, immunoglobuli, enoxaparin, +ve RT-PCR Poor feeding, reduced activity, reduced tone, sluggish
reflexes, seizures, fever
N/A 1(N/A), 7-day-old, term Diggikar et al., (24), India  2021 August 13, Case Report  
Elevated D-dimer, ferritin, CRP,
Echo: small coronary artery
2/18 Supportive therapy, mechanical ventilation,IVIG, LMWH, Inotropes, Steroids +ve IgG =17
+ve IgM=0
Cardiac, Hematologic,Respiratory,Gastrointestinal,Neurological, Cutaneous, Renal complications,  Fever/temperature instability +ve IgG =4
+ ve RT PCR=2
20(10/10), 1 to day 5, 27–38 weeks Pawar et al., (11), India , July 2 2021, Case Series  
Thrombocytopenia, leucocytosis,
Elevated CRP, PCT, Ferritin, D
Dimer, LDH, BUN, Creatinine, NT Pro BNP, IL-6
Arrhythmia, Dilated coronaries, Intracardiac thrombus, Shock/ cardiac dysfunction
Death Hydration, inotropes, packed red blood cells, fresh frozen plasma & platelets transfusion, antibiotic, furosemide, steroids +ve IgM
-ve RT-PCR
Tonic, mildly hypoactive, dehydration, vomiting, fever, jaundice, tachycardia, oliguria, abdominal tenderness, shock, ileal necrosis and ischemia, generalized
edema, maculopapular rash, gastrointestinal complications, cardiopulmonary arrest
-ve RT-PCR 1(female), 21days, term Skafi et  al., (25), Lebanon 2021.06.06, Case Report  
BUN , creatinine, troponin, ferritin
Normal Echo  
Discharged Mechanically
ventilation, surfactant, antibiotics, nitric oxide (iNO), inotropic agents,
-ve IgG
-ve IgM
-ve RT-PCR
Mucocutaneous signs, rash,
hepatosplenomegaly, respiratory distress syndrome, bilateral intraventricular
+ve RT-PCR
+ve IgG
1(female),  at birth, Pre term (31+4weeks) Schoenmakers et al., (16) The Netherlands, 2021 May, Case Report  
Thrombopenia, leucopenia, elevated creatinine,  ferritin, D-dimers,
cardiac enzymes
pulmonary hypertension of the neonate, flattened
interventricular septum, tricuspid regurgitation,
patent ductus arteriosus , right-to-left shunt, enlarged left main coronary
artery (LMCA)
Discharged Continuous positive
airway pressure, mechanical ventilation, prostaglandin E1, dobutamine, NitricOxide, Antibiotics, fresh frozen plasma, IVIG, hydrocortisone
+ve IgG
-ve RT-PCR
Mild cyanosis, progressive respiratory distress, myocarditis, pulmonary hypertension +ve RT-PCR 1(female),  15min old, Pre term (36 weeks) Shaiba et al., (8), Saudi Arabia,, 2021 May 13; Case Report  
Thrombocytopenia, anemia, prolonged INR,
elevated procalcitonin, CRP, liver & Cardiac enzymes, metabolic acidosis,
duct-dependent cardiac lesion, dilated left ventricle, poor systolic function, widely patent ductus arteriosus, bidirectional
+ve RT-PCR 1(female), at birth, Pre term (32 weeks)  
Grunting, respiratory
Nasal CPAP, NIMV, Antibiotics, IVIG, hydrocortisone  
-ve IgG
-ve IgM
+ve RT-PCR
Leukocytopenia, lymphocytopenia, elevated ferritin, troponin, procalcitonin, liver enzymes, D-dimer  
Normal Echo  
Discharged Positive pressure ventilation,
intubation and
mechanical ventilation, ampicillin, cefepime, nitric oxide, surfactant, Acyclovir
-ve  RT PCR Fever, hypotonic , poor respiratory effort +ve  RT PCR 1(male),  4-hour-old, Pre term (34 +6/7) McCarty et al., (7), USA, 2021 April 1; Case Report  
Leukocytosis, metabolic acidosis, positive herpes simplex
Virus, elevated interleukin 6, TNF
severe pulmonary hypertension,
Discharged Supportive care,
mechanical ventilation,
inotropic support,milrinone , diuretic antibiotics, IVIG, methylprednisolone , heparin, Calcium, vitamin C, vitamin D,  fluid and electrolyte management
+ve IgG
-ve RT-PCR
Drowsy, hypotension,
Erythema, tachypnoea,
chest retractions,
cool peripheries, delayed capillary refill, Hepatomegaly, cardiomegaly, heart failure, systemic hypoperfusion  cardiogenic shock
+ve RT-PCR
+ve IgG
24-day-old, term
Kappanayil et al., (21), India, 2021 April 1, Case Report  
Metabolic acidosis,
elevatedCRP, BUN,
creatinine ,
,cardiac enzymes
N-terminal-pro-B-type natriuretic peptide,
troponin T
Echo: biventricular dysfunction  
Discharged Mechanical ventilation with 100% oxygen, Sildenafil, Dexamethasone,
Dopamine, Furosemide,
Tazobactam/Piperacillin, intravenous fluids, Meropenem
+ve IgG
-ve IgM
-ve RT-PCR
Respiratory distress, cyanosis, feed intolerance, large aspirates prefeed,
increasing abdominal girth and vomiting; vasculitic
rash, Persistent Pulmonary Hypertension, early
necrotizing enterocolitis
-ve  RT PCR
+ve IgG
1(male),  4-hour-old, term Borkotoky et al., (14), United Kingdom ,2021 April 1, Case Report  
Bilateral ground glass opacities considered,
Echo;consistent with
moderate PPHN
Discharged Antibiotic + veIgG
-ve  RT PCR
Fever, jittery movements +ve IgG
-ve  RT PCR
1(female), 14days, term Charlesworth et al., (12) 2021, United Kingdom, Case Report  
Normal full blood count,CSF WBC= 347/mL with 65% neutrophils, RBC 105/mL,
positive leukocyte, nitrite, glucose, E. coli and Enterococcus in urine
Discharged Antibiotics, IVIG infusion, Aspirin, Dexamethasone, Methylprednisolone, immunomodulatory therapy (Anakinra) +ve  RT PCR Fever, tachycardia, bilateral pneumonitis, hepatosplenomegaly -ve  RT PCR 1(female), 14days, term Magboul et al., (26), Qatar, August 24, 2020, Case Report  
Lymphocytic leukocytosis, normocytic normochromic anemia, thrombocytopenia, Elevated CRP, hypoalbuminemia, hyponatremia, AST, , LDH, ALT, ferritin, Troponin, Natriuretic peptide test
normal coronary arteries and contractility  

* Negative
** Positive





The cause of MIS-N is the transmission or production of SARS-CoV2 antibodies in response to SARS-CoV2 infection. MIS-N may present following Early or Late-onset infections (13);

  • Early-onset infection: SARS-CoV2 antibodies can vertically transmit from the infected mother to the neonate, or the antibodies could be potentially produced by the neonate in response to maternal viral infection. It has been shown seropositive neonates who were born to mothers with negative or positive COVID-19 tests (14). Morek et al. indicated more neonates with positive IgG antibodies compared to their mothers (19 vs. 9 neonates) (13). Charlesworth et al. demonstrated an active uteroplacental transport of IgG from an asymptomatic COVID-19 infected mother to her neonates (3.5-fold; 1.84 vs. 0.53 AU/mL) (12). The other study demonstrated that of 83 seropositive mothers associated with SARS-CoV-2, IgG antibody was detected in 72 neonates (15). Postnatal SARS-CoV-2 transmission may also occur through intrapartum exposure to the maternal birth canal and respiratory secretions or body fluids (13). An investigation showed positive SARS-CoV-2 RT-PCR tests in different collected samples of a mother (during delivery), including the oropharynx, blood, vagina, urine, maternal and fetal sides of the placenta; however, the results related to collecting samples of her symptomatic neonate were negative (16).
  • Late-onset SARS-CoV-2 infection: The late-onset neonatal COVID-19 defines as a diagnosis of illness beyond 5-7 days after birth. Close contacts with mothers and health staff were responsible for 26% and 52% of late-onset SARS-CoV-2 infections in newborns, respectively (3). Moreover, there are conflicting results regarding the possible transmission of SARS-CoV-2 through breastfeeding. A systematic review study reported a positive SARS-CoV-2 RNA in the breast milk of 9 infected breastfeeding mothers (17). The other study indicated negative SARS-CoV-2 and IgG, but positive IgM tests in the breast milk samples of 8 confirmed COVID-19 mothers (18). A narrative review study also presented that of 13 included studies, one article demonstrated RNA of virus, and the other detected IgG antibody in the breast milk samples (19).

Maternal or neonatal SARS CoV-2 infection results in the secretion of the IgG antibodies against virus protein. An excessive level of IgG antibodies was detected in MIS-N cases as a genetically susceptible group. IgG antibodies in these cases can bind to macrophages and neutrophil receptors, causing hypersecretion of pro-inflammatory agents and Multi Inflammatory syndrome in neonates (11).

MIS-N Signs and Symptoms

It has been reported that COVID-19 infected neonates present mild symptoms with a fast recovery because of passive transfer of antibodies, fetal hemoglobin properties, immature immune system, and low expression of Angiotensin-Converting Enzyme-2 (3). While, a few studies indicated devastating complications following COVID-19 infection among neonates (3, 13). By evolving new mutant strains (like βand δ), newborns are now presenting more severe symptoms (20). Recent studies reported MIS-N as a severe complication with various organ involvement. The clinical manifestations of MIS-N may mimic sepsis, prematurity, toxic shock syndrome, RDS, Kawasaki disease, necrotizing enterocolitis (NEC), myocarditis, meningitis/encephalitis, aortic thrombosis, ETC (Table 1). Persistent pulmonary hypertension and bilateral ground-glass opacities were reported in a neonate with MIS diagnosis by Sankaran et al. (3). Skafi et al. reported a poor outcome case with severe hemodynamic instability and gastrointestinal problems due to cardiogenic shock, coagulopathy, and necrosis of the ileum (25). Pawar also reported cardiovascular disorders including shock, ventricular dysfunction, prolonged QTc, Atrioventricular thrombosis, hypotension, elevated cardiac enzymes, and coronary artery abnormalities to be the most frequent (90%) presentation among 20 subjects with MIS-N (11). Thakur et al. reported an MIS neonate with dilated bowel loops, bowel wall edema, and NEC diagnosis (20). The MIS-N cases with meningitis/encephalitis-similar manifestations (fever, cough, convulsion, and jittery movements) were also presented by 2 case-report studies (12, 22). Neonatal multi-organ failures with severe myocardial problems, skin lesions, and erythema accompanied by hyperinflammatory responses were reported in a case by Kappanayil (21). A COVID-19 infected neonate was reported as an MIS case with lower limb gangrene due to spontaneous aortic thrombosis (23).



Diagnosis of MIS-N is challenging because of diverse signs and symptoms. In addition, as very limited evidence is existent, the diagnosis is still controversial and may be postponed in the MIS-N cases. Biochemical parameters were also confusing in the disease with multi-organ involvement and inflammatory responses that may cause misdiagnosis.
The results of included studies have delineated that besides the clinical presentations, detection of reactive anti-SARS-CoV-2 IgG antibodies could be a notable clue in MIS-N diagnosis (16, 21). Of 14 included studies, 10 case-report studies have shown high IgG titers in their cases (8, 12-14, 20-23). Pawar et al. have also indicated a positive IgG test (cut-off-index ≥1) in 17 out of 20 MIS-N cases (11). On the other hand, several studies have shown that this diagnostic criterion was not observed in their reported cases (24).
As data are shown in Table 1, a history of perinatal COVID-19 infection/exposure or detection of maternal, placental, amniotic fluid, and neonatal positive SARS-CoV-2 RT-PCR tests could be also beneficial for MIS-N diagnosis (21).
Abnormal clinical biomarkers including sepsis-like and inflammatory markers(lymphocytic leukocytosis, metabolic acidosis, elevated C-reactive protein: CRP, ESR, Ferritin, D-dimers, Procalcitonin, thrombocytopenia subsequent to thrombocytosis, neutropenia, neutrophilia, anemia, elevated interleukin-6, andinterferon type 1) with negative blood, urine and CSF cultures, or markers showing coagulopathy (elevated prothrombin, activated partial thromboplastin time, international normalized ratio), pulmonary complications (low oxygen saturation:SpO2, and acidosis), liver dysfunction (elevated transaminases, aspartate aminotransferase: AST and alanine aminotransferase), cardiac dysfunction (Troponin T, aminotransferase, CKMB, CPK, lactate dehydrogenase, N-terminal pro-brain natriuretic peptide: ProBNP), renal failure (hypoalbuminemia, hyponatremia, severe anemia, increased blood urea concentration, hyper creatinine with abnormal urine analysis by elevated WBC and protein in urine) and abnormal stool exam (occult blood) were the other significant findings that have been shown by the included studies (Table 1).
Echocardiogram findings in the reported cases were prolonged QTc, dilated coronary arteries with prominent and hyperechoic appearance due to viral myocarditis, left ventricle dilatation, global hypokinesia, aneurysm, and severe myocardial dysfunction (11, 16, 21, 24). Ground glass opacities have also been observed in a neonate reported by (14). Almost all included studies have demonstrated that the diagnosis of MIS-N could be confirmed with clinical improvement to treatment with steroids and immunoglobulin (11, 24).


Treatment and Outcome

The results of included studies have shown that of the total of 53 reported subjects in the present study, 4 neonates had poor prognoses and died. The other subjects were successfully managed, and the neonates completely recovered. All included case-report studies have demonstrated that besides supportive therapy (hydration, electrolyte balance, inotropic support, oxygen therapy, and mechanical ventilation), suppressing the autoimmune and inflammatory responses by immunoglobulin-IVIG and steroids (methylprednisolone, prednisolone, or dexamethasone), anti-platelet agents (aspirin), and anticoagulants (heparin, Enoxaparin, recombinant tissue plasminogen activator) were effective in the alleviation of MIS-N symptoms. Along with these medications, Remdesivir was given to a SARS-CoV-2-positive neonate with neurological manifestations and possible MIS-N (24). Symptomatic treatments like administration of antibiotic regimen, Sildenafil, Furosemide, packed red blood cells, and fresh frozen plasma were reported by the studies (14, 20, 25). A study by Magboul et al. has also indicated the effectiveness of Anakinraas, the second agent and interleukin-1 inhibitor besides IVIG and steroid for a neonate with hyper-inflammatory syndrome (26) (Table 1).
So far, clinical guidelines have been implemented based on the decisions of experts and multidisciplinary teams. In contrast, it seems that the management of MIS-N needs a large number of clinical trials, including neonates and pregnant women, to assess the benefits and risks of treatment modalities. In addition, vaccination of pregnant women would be another effective effort to prevent such an adverse outcome in neonates with the transmission of antibodies from their infected mothers.



The present study aimed to highlight the possibility of MIS-N as an infrequent but severe syndrome consequent of perinatal COVID-19 infection. The diagnosis is still controversial, but clinical suspicion and awareness regarding this immunological disease is of importance for early diagnosis. Varied and severe neonatal presentations along with detection of maternal or neonatal reactive anti-SARS-CoV-2 IgG antibodies, could be substantial clues in MIS-N diagnosis. A positive perinatal COVID-19 infection or exposure history can also help with the diagnosis. Besides supportive therapy and symptomatic treatments associated with affected organs, immunoglobulin-IVIG, steroids, anti-platelet agents, and anticoagulants were reported as effective therapies. On the other hand, the management of MIS-N needs a large number of clinical trials, including the neonates, to assess appropriate treatment modalities with benefits and risks.




This study was supported by the Tehran University of medical sciences (TUMS) and the Maternal Fetal and Neonatal Research Center. We acknowledge their kindly supports in this study.



This research has been supported by the Tehran University of Medical Sciences and health service as well as the Maternal Fetal and Neonatal Research Center.


Conflicts of Interest

The authors declared no conflict of interest.


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