Monkeypox in neonates: A narrative review on clinical presentations, vertical transmission, and treatment challenges

Abstract

Monkeypox (Mpox), a zoonotic infection caused by the Mpox virus, has re-emerged as a global public health concern, with unique implications for neonatal health. Although rare in newborns, cases of neonatal Mpox pose significant diagnostic and therapeutic challenges due to limited clinical data and the vulnerability of this population. This narrative review explores the pathophysiology, clinical presentation, diagnostic barriers, and therapeutic strategies associated with Mpox in neonates. Vertical and perinatal transmission have been identified, with some cases presenting with vesicular rashes, fever, lymphadenopathy, and systemic involvement such as respiratory or neurological complications. Diagnosis often relies on polymerase chain reaction testing, yet resource limitations and symptom overlap with other neonatal infections can hinder accurate identification. Antiviral treatments like tecovirimat and cidofovir are considered in severe cases, but dosing in neonates remains uncertain due to a lack of robust safety data. Supportive care, including hydration, fever management, and prevention of secondary infections, is critical. Breastfeeding decisions require individualized assessment due to the unknown risk of viral transmission through breast milk. Preventive strategies emphasize early isolation, surveillance, and infection control measures in neonatal care settings. The review highlights significant research gaps in understanding neonatal Mpox, especially concerning long-term outcomes and optimal treatment protocols. A coordinated global effort is essential to improve diagnostics, develop safe therapeutic options, and establish evidence-based guidelines tailored to neonates.

Key Words: Mpox in neonates; Vertical transmission of monkeypox; Congenital mpox; Neonatal monkeypox treatment; Clinical presentation in infants; Therapeutic challenges

Core Tip: Neonatal Monkeypox, though rare, presents significant diagnostic and therapeutic challenges due to limited data and clinical overlap with other infections. Vertical and perinatal transmission pathways raise concerns for early-life vulnerability. This review highlights the urgent need for age-specific antiviral protocols and evidence-based guidelines for neonatal management.

INTRODUCTION

Monkeypox (Mpox) is a zoonotic illness caused by the Mpox virus (MPXV), a member of the Orthopoxvirus genus[1]. In 2022, a global Mpox outbreak (formerly called Mpox) began in multiple European and American nations, swiftly spreading to more than 100 countries and territories. The World Health Organization (WHO) declared the outbreak a global public health emergency in response to the rapid spread of the MPXV[2] In African countries where Mpox is endemic, the virus has also affected pregnant individuals, resulting in perinatal death rates reaching up to 75%[3]. Mpox infections are uncommon in neonates, particularly with the current circulating clade IIb variant. Nonetheless, when a neonate presents with a vesicular rash, Mpox should be included in the differential diagnosis. This consideration should be made alongside other conditions, such as varicella-zoster virus (VZV), herpes simplex virus (HSV), bacterial skin infections, and bacterial sepsis, especially if there is a family history of similar rashes[4].

Further research is required to identify the clinical issues associated with congenital and neonatal Mpox infections[4]. Global interest is needed to evaluate further the pathophysiology and the gap in understanding the clinical manifestations and outcomes of infections like Mpox in neonates. The primary objective is to highlight the clinical presentations, treatment challenges, therapeutic strategies, and outcomes of Mpox in neonates, as the existing literature has scattered and limited data on this topic.

MPXV: OVERVIEW AND PATHOPHYSIOLOGY IN NEONATES

Mpox is a double-stranded DNA virus with an envelope, classified under the Orthopoxviridae genus. This group also includes the highly lethal variola virus, responsible for over 300 million deaths globally from smallpox. Other viruses in this genus include vaccinia virus, cowpox virus, camelpox virus, and ectromelia virus (also known as mousepox). The MPXV is categorized into two main clades: Clade I (previously known as the Congo Basin Clade) and Clade II (formerly the West African Clade). Clade II is further divided into Clade IIa and Clade IIb, with the ongoing global outbreak being attributed to Clade IIb[5]. The first recorded case of human Mpox occurred in 1970, involving a 9-month-old infant who was admitted to Basankusu Hospital in the Equatorial Province of what is now the Democratic Republic of Congo. Initially suspected to have smallpox due to the lack of vaccination, the child was later confirmed to be infected with the MPXV[3]. The clinical symptoms of human Mpox are shaped by the method of exposure, the specific strain and amount of the virus involved, and the host's immune response. In general, individuals with advanced HIV infection, children under 5 years of age, and pregnant women are likely to experience more severe illness and have higher case fatality rates[6]. Human-to-human transmission of Mpox occurs through direct contact with lesion exudates, bodily fluids, or respiratory droplets, as well as through indirect contact with contaminated surfaces and objects. Mpox can also be transmitted vertically and may potentially spread through breastfeeding[7].

After the virus replicates at the site of entry, it moves to nearby lymph nodes. Following an initial phase of viremia, the virus may then spread to other organs, where further replication and secondary viremia take place, often accompanied by fever. Eventually, the virus reaches the skin, leading to the development of the hallmark pock-like rash. The documentation of a stillbirth caused by placental and fetal infection with the MPXV now classifies it as one of the "Other" agents in the TORCH group of infections[3]. One of the key mechanisms involves the transmission of the MPXV from mother to fetus following maternal viremia, where the virus enters the placenta via the uterine blood supply. This hematogenous route of transmission likely led to the transplacental infection observed in a stillborn fetus infected with the MPXV[3].

CLINICAL MANIFESTATION OF MPOX IN NEONATES

In neonates, Mpox can exhibit unique clinical features distinct from those in older children and adults. The incubation period for Mpox—the interval between exposure to the virus and the onset of symptoms—typically ranges from 5 to 21 days, with most individuals developing symptoms between 7 and 14 days post-exposure. This timeframe is generally consistent across various age groups, including neonates[8,9]. In neonates, the presentation of Mpox can vary. For instance, a case study from Brazil reported a newborn developing a vesicular rash on the scalp and thorax on the ninth day of life. However, the exact timing of exposure in this case was not specified, making it challenging to determine the precise incubation period. In Florida, a 4-month-old infant developed Mpox symptoms after six weeks of daily close contact with an infected caregiver, suggesting an incubation period within the expected range[10]. Following this incubation phase, the disease typically progresses to a prodromal stage, characterized by nonspecific symptoms, including fever, fatigue, and lymphadenopathy. This prodromal phase usually lasts between 1 and 4 days[11].

Early indicators in newborns commonly include a widespread papulopustular rash, fever, and lymphadenopathy. Lesions typically progress in stages, beginning as flat spots (macules), then evolving into raised spots (papules), followed by the formation of small, fluid-filled blisters (vesicles), and ultimately developing into pustules before crusting over. This rash progression, as observed in a case involving a 10-day-old United States infant, resembles the Mpox presentation in adults but is especially concerning in neonates due to their vulnerability to severe symptoms[12,13]. Fever often accompanies the rash in neonatal Mpox cases, with some infants also showing lymphadenopathy. These early symptoms can clinically mimic other viral infections, making diagnosis challenging. In one case, a prompt diagnosis was achieved when the infant's mother had recently had MPX, emphasizing the role of family history in identifying MPX in newborns[14]. Dermatological manifestations in neonates with mpox commonly present with a generalized rash that progresses through characteristic stages. Lesions typically begin as macules and evolve into papules, vesicles, and pustules, eventually scabbing over. These papulopustular lesions are deep-seated and firm, distinguishing mpox from other rashes in neonates[12,14]. A notable case in Brazil involved a newborn who developed a vesicular rash on the scalp and thorax by the ninth day of life. Polymerase chain reaction (PCR) testing of the vesicular fluid confirmed MPXV DNA, underscoring the importance of considering Mpox in the differential diagnosis of neonatal vesicular rashes, especially with a pertinent family history[8].

Clinical manifestations of Mpox in neonates can involve multiple systems, often with dermatological symptoms and, in some cases, respiratory, gastrointestinal, and neurological involvement. The disease spectrum in neonates ranges from asymptomatic cases to severe, systemic illness.

In some cases, newborns may experience respiratory symptoms, such as difficulty breathing, which could signal a severe progression involving respiratory distress. The potential for respiratory transmission of MPXV has been a subject of investigation. While laboratory experiments have demonstrated the initiation of MPXV infection via respiratory routes in animal models, human-to-human respiratory transmission appears to be low. Environmental studies have detected airborne MPXV, but real-life outbreak reports suggest that transmission is predominantly associated with close contact. Nonetheless, respiratory symptoms, including severe manifestations such as acute respiratory distress syndrome, have been observed in some cases[15].

Gastrointestinal symptoms, including vomiting and diarrhea, have also been reported in infants, although they are less frequent. A neonate presented with ocular involvement alongside skin lesions, highlighting the virus's potential to affect multiple organ systems[5].

Neurological involvement is rare in neonates but may include irritability or seizures in severe cases[13]. Mpox, caused by the MPXV, is an emerging zoonotic disease that has garnered global attention due to its increasing incidence. While the clinical presentation in adults is well-documented, reports of mpox in neonates are scarce, particularly concerning neurological manifestations. This narrative review aims to elucidate the potential neurological symptoms of mpox in neonates, drawing on accessible research and case reports[16]. A systematic review identified instances of encephalitis and seizures among children infected with MPXV, highlighting the virus's neuroinvasive potential. Notably, a 28-day-old infant in Nigeria developed encephalitis following mpox infection, underscoring the vulnerability of neonates to severe neurological outcomes[17]. The exact mechanisms by which MPXV affects the neonatal nervous system remain unclear. However, parallels with other orthopoxviruses suggest potential pathways for further investigation. Mpox hematogenously spreads through the bloodstream, crossing the immature blood-brain barrier in neonates. It directly invades via peripheral nerves, similar to the behavior of VZV[16].

The severity of mpox in neonates varies widely. Asymptomatic cases may occur, particularly in individuals with a low viral load or those who have developed maternal antibodies. Mild to moderate cases exhibit skin symptoms and mild systemic signs, which are typically managed with supportive care. Severe cases present with a widespread rash, systemic symptoms (fever, lethargy), respiratory distress, or neurological issues, often requiring antiviral treatment, such as tecovirimat, to prevent complications[12].

Distinguishing Mpox from infections like varicella and bacterial conditions can be difficult due to overlapping symptoms, such as rashes. Mpox is a zoonotic disease caused by the MPXV, an orthopoxvirus similar to the variola virus responsible for smallpox. Neonatal Mpox can result from vertical transmission during pregnancy or perinatally through close contact after birth. Clinically, mpox typically presents with a prodromal phase characterized by fever, malaise, and lymphadenopathy, followed by a centrifugal rash that progresses from macules to papules, vesicles, pustules, and ultimately to crusts. Lymphadenopathy is a distinguishing feature of mpox compared to other vesiculopustular diseases. Diagnosis is confirmed through PCR testing of lesion samples[9,18]. VZV infection in neonates can occur congenitally or perinatally.

Congenital varicella syndrome arises from maternal infection during the first or early second trimester, leading to limb hypoplasia, cutaneous scarring, and neurological anomalies. Perinatal varicella, resulting from maternal infection between 5 days before and 2 days after delivery, poses a high risk of severe neonatal disease due to the lack of transplacental antibodies. Neonatal varicella presents with a generalized vesicular rash without preceding lymphadenopathy. Diagnosis is primarily clinical, supported by PCR or direct fluorescent antibody testing of lesions[19]. Bacterial infections, such as congenital syphilis and listeriosis, can also present with skin manifestations in neonates. Congenital syphilis may cause symmetrical pustular lesions on the palms, soles, and other areas, accompanied by systemic signs like hepatosplenomegaly and anemia. Diagnosis involves serologic testing and direct detection of Treponema pallidum in lesions. Listeriosis, caused by Listeria monocytogenes, can lead to septicemia and meningitis in neonates, sometimes presenting with a diffuse rash of maculopapules, vesicles, or pustules. Blood or cerebrospinal fluid cultures confirm the diagnosis[18].

Mpox lesions are firm and deep, progressing through distinct stages, whereas varicella lesions are more superficial and appear in various stages simultaneously[20,21]. PCR is a key diagnostic tool for confirming mpox, but its availability can be limited in resource-poor settings, posing challenges for its widespread use[21]. Additionally, some studies suggest that clinicians may struggle to identify Mpox lesions in comparison to varicella, especially in cases where the lesion stages are unclear.

DIAGNOSIS AND LABORATORY FINDINGS

Accurate and timely diagnosis is essential for effective management and control of mpox outbreaks. The primary diagnostic methods include PCR and serological assays. However, diagnosing Mpox in neonates presents unique challenges due to the limitations inherent in these testing modalities[22].

PCR is the gold standard for detecting MPXV DNA due to its high sensitivity and specificity. It enables the identification of viral genetic material in various specimen types, including skin lesions, blood, and respiratory secretions. A systematic review and meta-analysis reported pooled sensitivity and specificity estimates of 99% and 100%, respectively, in scoring diagnostic accuracy in detecting mpox infections[23].

Serological assays detect antibodies produced in response to MPXV infection, providing insights into exposure and immune response. Techniques such as enzyme-linked immunosorbent assays and immunofluorescence assays are employed to identify IgM and IgG antibodies. IgM antibodies typically indicate recent infection, while IgG antibodies suggest past exposure or vaccination. However, the utility of serological tests is limited by cross-reactivity among orthopoxviruses, which complicates the differentiation between MPXV and other related viruses[1].

Laboratory abnormalities include alterations in the complete blood count, such as leukocytosis or lymphopenia, as well as elevated liver function tests and inflammatory markers, which may indicate multisystem involvement or a severe progression of the infection.

Neonates with Mpox may exhibit hematological abnormalities, including anemia, leukocytosis, leukopenia, and thrombocytopenia. These findings are not unique to mpox and can overlap with other neonatal infections. For instance, in neonatal sepsis, anemia is observed in approximately 49% of cases, while thrombocytopenia occurs in about 44.7% of affected neonates[24].

Elevations in liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), may indicate hepatic involvement in neonatal infections. A study analyzing liver function abnormalities in children reported median ALT and AST levels of 367 U/L and 274 U/L, respectively, in cases of nonspecific hepatitis[25].

Markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate are commonly elevated in neonatal infections, reflecting systemic inflammation. However, their specificity is limited, as they can be elevated in various inflammatory conditions. Advancements in laboratory medicine have introduced novel biomarkers, such as soluble CD14 subtype (presepsin) and lipopolysaccharide-binding protein, for the early detection of neonatal sepsis[26].

Abnormal liver function tests, such as elevated levels of AST and ALT, can signal liver stress or failure, which is often seen in severe infections. Elevated inflammatory markers—such as CRP, procalcitonin, and interleukins (like interleukins-6)—serve as biomarkers to help detect systemic inflammation and early immune responses, and they are essential in differentiating viral from bacterial infections. This approach is commonly used in diagnosing and managing neonatal sepsis, which shares similarities with mpox presentation in infants[27].

Mpox diagnostics in neonates are challenging due to the limited availability of specific testing options and overlapping clinical features with other neonatal infections, such as bacterial sepsis and viral rashes (e.g., varicella). The scarcity of specialized diagnostic tools for Mpox in newborns hampers the timely and accurate identification of the infection. This limitation is particularly pronounced in regions with limited laboratory resources, where access to advanced molecular testing is minimal[28].

Diagnosis usually involves PCR testing, but in many cases, this test might only confirm a general orthopoxvirus without specifying Mpox. Neonates with mpox may present symptoms similar to those of other infections, making differential diagnosis challenging. Key symptoms, such as rash, fever, and lymphadenopathy, can lead to initial misclassification, so accurate differentiation requires comprehensive clinical assessments, often in conjunction with family history, especially if a close contact has Mpox. Advanced diagnostic methods, such as sequencing, provide precision but are typically limited and may not be feasible for routine neonatal screening. Given the overlap of symptoms and specific testing limitations, clinicians must rely on a combination of clinical history, symptom progression, and access to PCR testing when feasible to confirm a diagnosis of mpox in neonates[20].

TREATMENT CHALLENGES IN NEONATES

The treatment of Mpox in neonates presents several complexities, particularly due to the limited antiviral options available. There is no Food and Drug Administration-approved medication specifically for Mpox, and most treatments are considered investigational. Tecovirimat, an antiviral developed for smallpox, is currently used in severe cases, but its safety and efficacy in neonates remain under investigation. Dosing for neonates, especially those under 13 kg, is not well-established, making age-appropriate dosing a challenge. Additionally, intravenous tecovirimat may pose risks such as nephrotoxicity, especially in neonates, so balancing treatment efficacy with safety concerns is essential[13,29]. The general limitations in neonatal antiviral treatments stem from a lack of clinical trial data for this age group, as well as concerns regarding side effects like renal toxicity from certain medications. In the case of severe Mpox, such as when the infant is at risk of complications like encephalitis or respiratory distress, alternative antivirals like cidofovir may be considered. Still, these also carry potential risks like liver and kidney toxicity. The immature immune system of neonates plays a crucial role in how effectively they can respond to infections like Mpox. This immune immaturity impacts the efficacy of treatments, as neonates may not mount a sufficiently strong immune response to combat the virus without support.

Moreover, immune dysregulation can lead to complications, particularly in severe cases, where the immune system may be unable to control viral replication adequately. Neonates rely on maternal antibodies (particularly IgG transferred through the placenta) for initial immune protection. Still, preterm infants or those with weakened immune responses may have lower antibody levels, increasing vulnerability to infections. Maternal antibodies, especially IgG transferred transplacentally, provide crucial passive immunity to newborns. However, the efficiency of this transfer can be compromised in preterm infants or in cases where maternal infections alter antibody glycosylation patterns, resulting in decreased antibody functionality and transfer efficiency[30].

Additionally, the neonatal immune system suppresses inflammatory responses to avoid overreactions to benign antigens, which can further limit the response to pathogens and vaccines. This immaturity results in complications, as standard antiviral therapies often lack age-appropriate formulations and must be carefully adjusted to avoid effects. Managing MPXV in breastfeeding mothers presents unique challenges due to the uncertainty about virus transmission through breast milk and the close contact required for breastfeeding. Although it's not confirmed whether Mpox can be transmitted via breast milk itself, the risk of transmission from mother to infant through skin-to-skin contact is a significant concern. Consequently, both the WHO and the Centers for Disease Control and Prevention recommend a case-by-case assessment of breastfeeding decisions for mothers with mpox, taking into account the mother's and the child's needs, as well as the available alternatives[31]. Mothers with MPX are advised to follow protective measures if they continue breastfeeding. This includes covering any lesions, particularly if present on or near the breast, wearing gloves and protective clothing, washing hands thoroughly, and using a mask. For mothers who must interrupt breastfeeding due to the severity of their illness, expressed milk may be considered. However, milk from an affected breast should be discarded if lesions are present. Decisions should prioritize the health of both the infant and the mother, weighing the benefits of breastfeeding against the risks of transmission.

THERAPEUTIC OPTIONS FOR NEONATES WITH MPOX

Mpox, previously known as Mpox, is a zoonotic disease caused by the MPXV, an orthopoxvirus similar to the variola virus responsible for smallpox. While Mpox primarily affects adults, neonatal cases, though rare, present unique challenges due to the vulnerability of this population and the limited data on effective treatments. This review focuses on the antiviral agents currently considered for treating Mpox in neonates[32].

Neonates are particularly vulnerable to viral infections due to their immature immune systems. Antiviral therapies, such as Tecovirimat and Cidofovir, have been explored for use in this population. This review examines the applicability, efficacy, safety profiles, and dosing challenges of these agents in neonates[33].

Tecovirimat

Tecovirimat, initially approved for the treatment of smallpox, targets the orthopoxvirus VP37 envelope protein, thereby blocking viral maturation and spread. Although its effectiveness in adults is well established, there is limited information about its safety and efficacy in neonates. Additional studies are needed to develop suitable dosing regimens and better understand potential side effects in this high-risk group.

Efficacy and safety profiles

In immunocompromised pediatric patients, cidofovir has demonstrated efficacy against resistant viral infections. However, its use is limited by significant nephrotoxicity, manifesting as proximal tubular dysfunction. Concomitant administration of probenecid and adequate hydration can mitigate renal toxicity. Other adverse effects include neutropenia and ocular hypotonia[34-36].

Dosing challenges

Due to limited pharmacokinetic data, determining the optimal dosing regimen for cidofovir in neonates is challenging. Studies suggest that modified dosing strategies, such as administering 1 mg/kg thrice weekly, may reduce nephrotoxicity while maintaining antiviral efficacy. Nonetheless, individualized dosing based on renal function and close monitoring are imperative[34].

Supportive care plays a pivotal role in managing patients with infections, focusing on interventions such as adequate hydration, oxygen therapy, fever control, and the prevention and treatment of secondary bacterial infections.

Hydration

Maintaining proper hydration is essential for patients with acute respiratory infections. A systematic review assessed the impact of increased fluid intake on the duration and severity of symptoms in such patients. The review highlighted the need for further research to establish clear guidelines, as the benefits and potential adverse effects of increased fluid intake remain uncertain[37].

Oxygen supplementation

Oxygen therapy is critical in treating sepsis and preventing associated complications. A review discussed the role of oxygen therapy in sepsis management, noting that while hyperoxia may have beneficial effects, it is essential to monitor oxygen levels carefully to avoid potential toxicity[38].

Fever management

Controlling fever in critically ill patients with infections is a subject of ongoing debate. A narrative review examined various strategies for fever management in intensive care settings, emphasizing that while fever can be a natural defense mechanism, its modulation should be considered based on individual patient conditions and the underlying cause of the infection[39].

Management of secondary bacterial infections

Addressing secondary bacterial infections is crucial in the care of patients with viral infections, such as coronavirus disease 2019 (COVID-19). A multicenter, nested case-control study evaluated treatment strategies that influence the risk of secondary bacterial infections in COVID-19 patients. The study found that early antiviral use and supplemental oxygen decreased the risk of such diseases, highlighting the importance of timely interventions[40].

PREVENTION AND PUBLIC HEALTH STRATEGIES

For neonatal Mpox, strict isolation strategies are crucial. Healthcare providers caring for neonates should follow infection control protocols to prevent cross-contamination. This includes using personal protective equipment, such as gloves, gowns, and masks, and ensuring that neonates born to mothers infected with the virus are placed in isolation. It is also essential to educate staff on the proper handling and care of newborns to avoid exposure to the virus, which can cause severe outcomes in neonates[41]. Surveillance and rapid diagnosis are crucial for managing neonatal Mpox, especially in endemic regions. Early detection can significantly impact the control of outbreaks and the clinical management of infected infants. With the emergence of Mpox cases in various parts of the world, the importance of efficient surveillance systems and accurate diagnostic methods cannot be overstated.

Diagnostic tools, such as PCR tests, are essential for confirming the presence of the virus, particularly when neonates present with symptoms similar to those of other viral infections, such as varicella or bacterial infections[42]. A comparative overview of Monkeypox and other neonatal infections is presented in Table 1. The availability of these tests in resource-limited settings remains a challenge; however, the prompt identification of Mpox can facilitate early interventions, thereby reducing the likelihood of severe outcomes. Enhanced surveillance in neonatal care settings, such as the Neonatal Mpox Surveillance Initiative, the Enhanced Mpox Monitoring Program for Newborns, or the Neonatal Orthopoxvirus Response and Tracking System, coupled with rapid diagnostics, plays a key role in preventing widespread transmission and ensuring timely clinical care.

Table 1 Comparing Monkeypox to other neonatal infections.

Feature	Monkeypox	Congenital varicella	Neonatal HSV	Bacterial sepsis
Agent	Orthopoxvirus (MPXV)	Herpesvirus (VZV)	Herpesvirus (HSV1/2)	Various bacteria (e.g., Escherichia coli)
Incubation	5-21 days	10-21 days	About 5-21 days	Hours-days
Rash	Deep, firm pustules in synchronous stages	Superficial vesicles at mixed stages	Grouped vesicles, may ulcerate	Often absent or nonspecific
Mode of transmission	Close contact; perinatal/vertical	Transplacental or perinatal	Transplacental; peripartum/postnatal	Vertical, nosocomial
Key lab	PCR for MPXV DNA	PCR/DFA for VZV	PCR for HSV	Blood/CSF cultures
Treatment	Supportive; tecovirimat	Acyclovir	Acyclovir	Empiric broadspectrum antibiotics
Prognosis	Variable, better in supportive care	Risk of mortality/morbidity	Poor if untreated, improved with early therapy	Depends on pathogen and prompt treatment

PCR: Polymerase chain reaction; MPXV: Monkeypox virus; DFA: Direct fluorescent antibody; VZV: Varicella-zoster virus; HSV: Herpes simplex virus; CSF: Cerebrospinal fluid; CBF: Cerebral blood flow.

RESEARCH GAPS AND FUTURE DIRECTIONS

Although infections in children and teenagers in the United States are still relatively rare, pediatric emergency and urgent care providers need to be aware of the clinical characteristics, treatment options, and preventive measures for this emerging infectious disease[43]. Additional studies are required to identify the clinical challenges associated with congenital and neonatal Mpox infections[4]. There is a significant lack of research on Mpox infections in neonates. Greater global attention is essential to deepen understanding of the disease's pathophysiology, clinical presentation, and outcomes in this age group. The specific symptoms and course of Mpox in newborns remain largely unclear. With only a small number of reported cases, further investigation is crucial to determine whether the clinical signs differ from those seen in older children and adults. Moreover, information is scarce regarding the potential long-term effects of Mpox on neonatal health, particularly considering the distinct nature of their developing immune systems[12].

The frequency of mother-to-child Mpox transmission during pregnancy or childbirth is still uncertain, and the effectiveness of preventive measures for neonates requires further study. Research is essential for a clearer understanding of the mechanisms of vertical transmission and for developing preventive strategies, including evaluating vaccination options for newborns at high risk. Clinical trials are necessary to inform future directions and determine the treatment strategies and safety of antiviral drugs in neonates. Complete data on treatment outcomes and follow-up in neonates is also needed. However, ethical considerations may hinder research on populations like neonates.

CONCLUSION

In conclusion, Mpox can present with unique clinical features in neonates that differ from those observed in older children and adults. Early identification is critical, as the immature immune system of neonates may predispose them to more severe disease. Given this, clinicians should include Mpox in the differential diagnosis of any neonatal vesicular lesions and promptly use PCR testing of lesion fluid to confirm the diagnosis. Strict contact isolation and precautions are warranted to prevent spread in nurseries and healthcare settings. Currently, Tecovirimat—an antiviral originally developed for smallpox—is being used in severe cases under compassionate use protocols. However, critical knowledge gaps persist. No clinical trials have yet evaluated the safety or efficacy of Mpox therapeutics in neonates; therefore, evidence-based treatment recommendations for this age group are currently lacking. Studies are urgently needed on the mechanisms and frequency of vertical (transplacental or perinatal) transmission of MPXV. Equally important are long-term follow-up studies: The developmental and neurologic outcomes of infants who survive neonatal Mpox infection are unknown. Prospective cohort studies will be essential for defining any sequelae and guiding follow-up care. By emphasizing these points, we underscore that protecting newborns from Mpox will require both vigilant clinical practice (early recognition, testing, isolation, and appropriate therapy) and dedicated research into neonatal disease dynamics and long-term outcomes.