Authors: Nasibeh Hasani, Ahmadreza Haddadi, Ahmadreza Abedi, Parnia Mirzaei, Ali Haddadi
Categories: Case Report, Neonatal varicella, Herpes zoster in infancy, Varicella zoster virus (VZV), IVIG prophylaxis
Source: Journal of Medical Case Reports
Authors: Nasibeh Hasani, Ahmadreza Haddadi, Ahmadreza Abedi, Parnia Mirzaei, Ali Haddadi
Varicella infection during late pregnancy is uncommon but can lead to serious complications for the neonate, including neonatal varicella and, rarely, early-onset herpes zoster. Standard management includes postnatal separation, administration of intravenous immunoglobulin, and antiviral treatment when indicated. However, prophylaxis may not always prevent infection or reactivation, especially in cases where maternal immunity is absent.
In March 2024, a 35-year-old Iranian pregnant woman who developed varicella at 37 weeks of gestation presented. She was treated with oral acyclovir (400 mg three times daily), and cesarean delivery was performed 5 days later under strict infection control protocols. Serologic testing confirmed low maternal varicella zoster virus immunoglobulin G levels, indicating no prior immunity. The newborn, an early-term female (weight = 2860 g), was delivered healthy and admitted to the neonatal intensive care unit in isolation. On day 2 of life, she received 1 g of intravenous immunoglobulin (~350 mg/kg) as prophylaxis despite being asymptomatic. However, at 16 days of age, she developed vesicular lesions (typical varicella lesions) and was hospitalized and treated with intravenous acyclovir. She was later switched to an oral formulation. At 6 months of age, the infant presented with herpes zoster, despite no known contact with infected individuals. She was treated with oral acyclovir and recovered fully. No developmental delays or neurologic complications were observed at 1-year follow-up.
This case highlights that neonatal varicella can occur despite intravenous immunoglobulin prophylaxis and strict isolation, and early-onset herpes zoster may follow perinatal exposure. Close follow-up of exposed neonates is crucial, and further research is needed to better understand the protective efficacy of intravenous immunoglobulin and the mechanisms of early varicella zoster virus reactivation in infancy.
Varicella zoster virus (VZV), the main pathogen of both varicella (chickenpox) and herpes zoster (shingles), typically causes mild illness in children [1]. However, varicella infection during pregnancy, especially in the third trimester, can lead to serious complications for both the mother and the fetus or neonate [2]. The clinical consequences of maternal varicella depend significantly on both the timing of infection and the maternal immune status, particularly whether protective VZV antibodies are present. Infections occurring between 5 days before to 2 days after delivery are particularly dangerous, as they can result in neonatal varicella, which is associated with high morbidity and mortality if left untreated [3].
To reduce the risk of neonatal infection in high-risk exposures, guidelines recommend post-exposure prophylaxis with varicella zoster immune globulin (VZIG). In settings where VZIG is unavailable, intravenous immunoglobulin (IVIG) is considered an alternative [4]. Despite prophylaxis, breakthrough varicella infections can still occur. The use of acyclovir is standard for the treatment of symptomatic neonatal cases. Moreover, VZV can establish latency in sensory nerve ganglia and may reactivate later in life, causing herpes zoster [5]. Herpes zoster in infancy, especially in immunocompetent children, is rare and typically associated with in utero or early neonatal VZV infection [6].
Although isolated reports exist of neonatal varicella and early-onset zoster, cases involving both conditions in the same infant—despite standard prophylactic and isolation protocols—are uncommon. The current case highlights the complexity of managing perinatal VZV exposure, illustrating the potential for delayed onset neonatal varicella even after IVIG prophylaxis and rare reactivation as herpes zoster within the first year of life. This report aims to contribute to the limited body of literature on this clinical scenario and underscore the importance of long-term follow-up and evaluation of current prophylactic strategies.
A 35-year-old Iranian woman contracted varicella at 37 weeks of gestation. Serologic testing showed low levels of VZV immunoglobulin G (IgG), confirming primary infection and lack of pre-existing immunity. The mother was treated with oral acyclovir (400 mg three times daily) starting from the day of diagnosis and continued until delivery 5 days later. She was admitted to an isolation room in the obstetrics ward and underwent a cesarean section at the end of 37 weeks owing to rupture of membranes. The surgical team and operating room staff consisted of individuals with a history of prior varicella infection. After delivery, the operating room was thoroughly disinfected with 70% alcohol.
The neonate, a healthy early-term female with Apgar scores of 10, was immediately separated from the mother and admitted to an isolation room in the neonatal intensive care unit (NICU). The neonate showed no signs of varicella at birth. She weighed 2860 g at birth and received a single prophylactic dose of 1 g IVIG on day 2 of life, which corresponds to approximately 350 mg/kg. Breastfeeding was avoided during the 10-day separation period. After the tenth day of life, feeding with breast milk was provided indirectly using a breast pump and bottle feeding and the mother remained symptom free after the tenth day postpartum. A VZV polymerase chain reaction (PCR) test performed on the neonate’s blood on day 2 was negative.
At 16 days of age, the infant developed vesicular skin lesions consistent with varicella (Figs. 1, 2). A diagnosis of neonatal varicella was confirmed by a pediatric infectious disease specialist (no specific test was performed). The neonate was re-admitted to the NICU, isolated, and started on intravenous acyclovir. On the fourth day of hospitalization, owing to difficulty in establishing intravenous access, the treatment was switched to oral acyclovir. The infant was discharged with oral acyclovir syrup after clinical improvement.Fig. 1Varicella zoster virus lesions appeared on the infant’s scalp on day 16 after birthFig. 2Varicella zoster virus lesions on the infant’s chest and abdomen on day 16 after birth
The infant’s growth and neurodevelopment were normal over the following months. At 6 months of age, the child developed a cluster of papular vesicular lesions, consistent with herpes zoster (Fig. 3), despite no known contact with infected individuals. The diagnosis was confirmed by a pediatric specialist (no specific test was performed), and the child was treated at home with oral acyclovir (20 mg/kg/dose four times daily for 7 days = 3 mL per dose for 6 kg), resulting in full recovery.Fig. 3Clustered shingles (herpes zoster) lesions on the lower back of the infant at 6 months of age
The mother reported behavioral changes and nocturnal irritability in the child following the episode of herpes zoster. However, at 1 year of age, the child demonstrated normal growth and cognitive development without signs of developmental delay or neurological impairment.
Neonatal varicella is a rare but potentially life-threatening condition that occurs when maternal varicella develops near the time of delivery [4]. The most critical period is from 5 days before to 2 days after birth, during which the trans-placental transfer of maternal antibodies is insufficient to protect the newborn [7]. The estimated incidence of neonatal varicella in this window is low, but the mortality rate can reach up to 30% in untreated cases [8]. Hence, prophylactic administration of varicella zoster immune globulin (VZIG) or intravenous immunoglobulin (IVIG) and close monitoring are standard recommendations [9].
In this case, although the mother developed varicella at 37 weeks of gestation and underwent delivery at the end of that week under strict isolation protocols, the newborn received IVIG prophylaxis on day 2 of life, had no signs of infection at birth, and was separated from the mother. These steps align with best practice recommendations aimed at minimizing vertical or peripartum transmission. On day 2 of life, VZV PCR was negative in the neonate, raising the possibility of either vertical transmission with incubation or postnatal acquisition. However, a negative PCR at this early stage cannot rule out VZV infection. However, the infant developed symptomatic varicella at 16 days of life, suggesting that IVIG may have provided only partial or delayed protection, particularly in the context of absent maternal immunity, or that the infant was exposed to a low-level viral load in utero or immediately postpartum before isolation was complete.
While IVIG is often used when VZIG is unavailable, its effectiveness in preventing neonatal varicella is less clearly established [10]. Unlike VZIG, which contains high titers of specific anti-VZV antibodies, IVIG contains lower concentrations of VZV-specific immunoglobulins [11]. In addition, IVIG may not offer prolonged passive immunity, which could explain the delayed onset of disease in this infant. A report from a resource-limited setting emphasizes challenges in prophylaxis effectiveness [12]. This case supports the notion that prophylaxis may reduce the severity but not always prevent infection, particularly if maternal infection occurs very close to delivery.
The development of herpes zoster at 6 months in this infant adds another important dimension to the case. Herpes zoster in infancy is rare and usually occurs in children who had intrauterine or early neonatal varicella, often before the age of 12 months [13]. Similarly, benign herpes zoster has been reported in otherwise healthy infants following maternal infection in the third trimester, consistent with our patient’s uneventful neurodevelopmental outcome [14]. In this case, there was no known postnatal exposure, and the infant was otherwise healthy and there was no family history of immunodeficiency or chronic illness, which suggests reactivation of latent virus acquired during the neonatal infection.
It is notable that the infant had undergone non-invasive prenatal testing (NIPT) during the neonatal period, which showed no known genetic abnormalities. This supports the interpretation that her early-onset herpes zoster was unlikely due to an underlying congenital immunodeficiency or genetic syndrome affecting immune function. While NIPT is not designed to assess immune competence directly, the absence of genetic anomalies adds further weight to the view that the infant was otherwise healthy and immunocompetent at baseline.
The mechanism underlying early VZV reactivation in infants is not fully understood. Immaturity of the immune system and high-level viral exposure during the perinatal period may reduce the ability to maintain latency. Early antiviral treatment or passive antibody administration could also influence the host’s immune priming and latency dynamics.
The behavioral changes (such as night-time irritability) noted by the mother after zoster may point to subtle neurotropic effects of the virus, although no developmental delays or neurological deficits were observed during follow-up.
This case emphasizes the importance of long-term surveillance for infants with early-life VZV exposure, regardless of whether they are symptomatic initially. It also raises questions about the duration and efficacy of IVIG protection in neonates and highlights the need for improved strategies for managing perinatal varicella exposure.
A review of literature reveals few reported cases of both neonatal varicella and early herpes zoster in the same infant, particularly following prophylactic IVIG. This underscores the rarity and clinical significance of the presented case.
This case report is subject to several limitations. First, as a single case observation, it cannot establish causality or generalize the effectiveness or failure of IVIG prophylaxis in preventing neonatal varicella. Second, laboratory confirmation of VZV PCR was not performed for the mother and neonate during the herpes zoster episode, which would have strengthened the diagnostic certainty and timeline of viral exposure and reactivation.
In addition, there is a reliance on parental reporting of behavioral changes following herpes zoster, without formal neurodevelopmental assessment or neurological imaging. Although the child showed no delays at 1-year follow-up, long-term outcomes remain unknown and warrant further observation.
This case underscores the limitations of current prophylactic strategies in preventing neonatal varicella. Despite receiving a single dose of IVIG and maternal treatment with acyclovir, the newborn developed varicella at 16 days of life, followed by herpes zoster at 6 months. This highlights the importance of carefully evaluating maternal VZV immunity and considering individualized prophylaxis approaches in high-risk neonates.
Given the atypical progression in this case, close monitoring and long-term follow-up of neonates exposed to varicella in late pregnancy are essential. Further studies are needed to clarify optimal dosing, timing, and effectiveness of IVIG, as well as to better understand the mechanisms underlying early VZV reactivation in infancy.
Day −5 to 0 (before birth):
Mother develops typical varicella rash at 37 weeks gestation
Started on oral acyclovir 400 mg three times daily
No VZV IgG detected in maternal serum, confirming lack of prior immunity
Day 0 (birth):
Female neonate delivered via cesarean section at 37 + 6 weeks
Birth 2860 g; Apgar 10
Immediate postnatal isolation and NICU admission
No signs of infection at birth
*Day 2 of *
Received single dose of IVIG (1 g ≈ 350 mg/kg) as post-exposure prophylaxis
VZV PCR from serum was negative
Breastfeeding avoided during 10-day maternal isolation
*Day 16 of *
Developed typical vesicular rash consistent with neonatal varicella
Hospitalized and treated with intravenous acyclovir; later switched to oral due to intravenous access difficulty
Clinical improvement and discharged with continued oral acyclovir
*2–6 Months of *
Regular growth and development with no delays or complications observed
No new exposures to VZV reported
*6 Months of *
Presented with clustered vesicular rash on the back, diagnosed as herpes zoster
Treated at home with oral acyclovir (20 mg/kg/dose four times daily for 7 days = 3 mL per dose for 6 kg)
Mother reported nocturnal irritability but no other symptoms
*1 Year of *
Child showed normal growth and neurodevelopment
No neurologic deficits or behavioral abnormalities on follow-up