We can work on VZV infection causes two distinct forms of the disease

Insights from the literature show that VZV infection causes two distinct forms of the disease: chickenpox or varicella, and herpes zoster or shingles. Among pregnant women, primary infection with VZV has been reported to have significant systemic implications for both foetal and maternal health (Jones & Whittle, 2019; Levin et al., 2019; Trotta et al., 2018). Yet, the literature lacks consensus regarding a universal guideline on complications, management, and prevention of VZV infection among pregnant women. The purpose of this systematic literature review was to explore complications associated with varicella-zoster virus infection in pregnant women and to identify the most effective evidence-based management and preventive practices. In the current chapter, the discussion of findings is presented in the light of the formulated research aim and research questions, theoretical framework, and past studies that have been conducted on VCV infection in pregnant women. Further, the chapter discusses the implications for practice, research process, public health relevance, and suggestions for future research.

5.2. Implications of the Findings
The findings of the current systematic research have potential implications for nursing in terms of VZV infection management and treatment, and also for public health in terms of disease prevention. Undertaking the current systematic study focused on answering three research questions focused on identifying the complications associated with VZV infection in pregnant women, exploring appropriate management practices when providing care to pregnant women exposed to VZV infection, and understanding current prophylactic practices currently recommended in preventing and mitigating against varicella-zoster virus among pregnant women. Subsequent sections discuss the implications of findings obtained from obtained studies in the light of the three research questions pointing out areas of contention and convergence from the obtained studies and past literature.

RQ1 was created to help identify the following: What complications are associated with varicella-zoster virus infection in pregnant women? 

Findings showed that primary ZVZ infection during pregnancy has substantial complications for both the foetus and the mother (Nanthakumar et al., 2021; Ojide et al., 2015; Parente et al., 2018; Sarma, 2020). There is increased mortality and morbidity resulting from primary VZV infection due to maternal pneumonia and maternal varicella, while the foetus is exposed to a high risk of congenital varicella syndrome. By contrast, secondary infection due to latent VZV reactivation is limited to localised skin infection with a reduced risk of CVS (Mirinaviciute et al., 2019; Schafer et al., 2019; Sile et al., 2022; Swamy & Dotters, 2019). Although reactivation of VZV in pregnant women may not increase foetal deformities or mortality, shingles may lead to secondary complications that increase maternal morbidity.
In the majority of the affected patients with herpes zoster, there is skin manifestation within five days after the viral prodrome (Parente et al., 2018; Sarma, 2020). However, the viral symptoms are not uniform with some patients reporting weariness, fatigue, mild temperature, and diverse general clinical manifestations. The findings align with past studies which show that these symptoms are often misinterpreted as biliary colic, cholecystitis, myocardial infarction, or appendicitis (Nanthakumar et al., 2021; Shazly & Eltaweel, 2022). VZV reactivation and subsequent replication results in inflammation and necrosis in the affected sensory ganglia. On the skin, the patients manifest dermatomal zoster rash with pustular skin lesions and grouped papulovesicular (Elamin & Ahmed, 2013; Swamy & Dotters, 2019).
During the perinatal period, maternal zoster may not pose potential problems to infants since the newborns possess specific maternal IgG antibodies (Lachiewicz & Srinivas, 2019). Zoster appearance may also result in an antibody surge in the neonate from varicella (Mate et al., 2021; Vasileiou et al., 2018). However, researchers largely agree that the potential complication results from the viremic spread of VZV and when the mother is immunocompromised. The findings are in line with a prospective study of 382 women which showed that the risk of congenital varicella syndrome in infants increases due to congenital malformations especially after the mother had disseminated zoster during week 12 of gestation (Riordan, 2020).
The current research, however, observed some reports that intrauterine infection to the perineum, the labia minora and majora may pose a risk of infection (Horien & Grose, 2012; Inbaraj et al., 2021). However, there is no serological or clinical evidence of VZV infection in newborns whose mothers develop perinatal zoster (Mirinaviciute et al., 2019). The findings align with past observations that infants do not appear to be at risk of infection if herpes zoster occurs during or at the time of delivery (Ahn et al., 2016; Benoit et al., 2015). Despite several accounts of babies being born to mothers who had zoster in the first trimester of their pregnancies, no case had laboratory proof of intrauterine VZV infection (Inbaraj et al., 2021; Lachiewicz & Srinivas, 2019; Swamy & Dotters, 2019).
Findings showed that researchers and practitioners largely agree that susceptible pregnant women who contract varicella are at risk of more complications when they develop pneumonia, a severe lung infection (Nanthakumar et al., 2021; Ojide et al., 2015). Inflammation or encephalitis of the brain tissue may occur in a small number of pregnant women with varicella. Maternal pneumonia may result in an increased risk of mortality or serious morbidity due to encephalitis and cerebellar ataxia (Mirinaviciute et al., 2019; Nanthakumar et al., 2021). Further complications may also cause foetal varicella syndrome in addition to varicella infection of the newborns, which includes neonatal varicella and congenital varicella syndrome (Ojide et al., 2015; Parente et al., 2018).
Varicella pneumonia is potentially life-threatening with an increased risk of miscarriage or premature labour (Elamin & Ahmed, 2013; Ghosh & Chaudhuri, 2013). The time will affect the baby’s dangers. Congenital varicella syndrome has a 0.5–1% chance of developing in a baby if varicella manifests within the first 12 weeks of pregnancy (Horien & Grose, 2012; Inbaraj et al., 2021). While a baby has a 2% chance of developing birth abnormalities if the virus is caught between weeks 13 and 20 (Liang et al., 2016; Mirinaviciute et al., 2019). Affected infants may have underdeveloped legs and arms, incomplete brain development, and eye inflammation (Nanthakumar et al., 2021; Ojide et al., 2015). While researchers agree that VZV infection may have various complications, the clinical manifestations or symptoms may vary by the case from mild to severe.

RQ2 was created to help uncover the following: What appropriate management practices are most appropriate when providing care to pregnant women with the varicella-zoster virus?
Findings showed that while the risk of complications, such as PHN may increase among pregnant women, the disease management process is often inadequate (Bapat & Koren, 2013; Gabutti et al., 2019; Gaymard et al., 2018). From an obstetrical standpoint, the main difficulties of maternal HZ are reassuring the patients, identifying appropriate treatment, and subsequent prevention of further transmission (Kim et al., 2013; Levin et al., 2019; Mehta, 2016). While herpes zoster may not impact pregnant outcomes, it has potential implications for maternal morbidity since complications are debilitating and severe.
Considering the likelihood of serious sequela of herpes zoster, there is a need to hospitalize affected mothers. When outpatient management is chosen, there should be clear parameters for evaluation and check-ups mostly concerning respiratory symptoms (Hayward et al., 2018; Jones & Whittle, 2019). In line with HBM theory, patients who feel supported and closely assisted when accessing care are likely to be proactive in seeking healthcare support services (Jones et al., 2014). Consensus in the literature largely advocates the need for early treatment for all pregnant women exposed to herpes zoster to accelerate the healing of cutaneous lesions, and reduce the severity and duration of pain.
Depending on the severity, VZV infection management largely focuses on using topical treatments, depressants, anticonvulsants, opioids, vaccination, and surgery in severe cases. Three common antiviral drugs in most extracted studies include acyclovir, valacyclovir, and famciclovir. The first line of treatment is 800mg of oral acyclovir five times daily for 7 to 10 days (Mirinaviciute et al., 2019; Sarma, 2020; Wutzler et al., 2021). Findings from this research echo observations from past studies that acyclovir substantially shortens the time of viral shedding enhances healing, reduces the duration and severity of acute pain, and reduces the risk of PHN pain (Gabutti et al., 2019; Gaymard et al., 2018). However, insights from collected studies show that acyclovir has low bioavailability requiring frequent dosing to achieve desired therapeutic impact, but increases side effects.
Famciclovir and valacyclovir have up to 3–5x the serum levels of acyclovir and have a longer half-life (Wutzler et al., 2021). Thus, using the medications may not require frequent dosing. However, given the limited studies on the use of the two drugs in pregnant women, there is no specific recommended dose necessitating the need for further research on the topic (Ojide et al., 2015; Parente et al., 2018). The scarcity of clinical and case report data concerning the use of antivirals in pregnancy has also been reported for acyclovir. However, the clinical practice with the use of antivirals in the treatment of herpes simplex and varicella pneumonia infection is suggestive of these medications’ effectiveness in treating herpes zoster (Liang et al., 2016; Mirinaviciute et al., 2019).
Findings from a large nationwide cohort study showed no association between VZV exposure and acyclovir, famciclovir, or valacyclovir, especially in the first trimester and possible birth defects (Johnsson et al., 2019; Shazly & Eltaweel, 2022). The effectiveness of antiviral therapy depends on how quickly it is administered. As soon as feasible following the beginning of skin symptoms—ideally, within 48–72 hours—antiviral medication should be started. Antiviral medication should be started in all immunocompromised herpes zoster patients, even if they arrive later than 72 hours (Mirinaviciute et al., 2019; Ojide et al., 2015). Whereas oral therapy is sufficient in the majority of straightforward cases of herpes zoster, systemic therapy is necessary when specific clinical symptoms are present (Nanthakumar et al., 2021). Patients who have mucosal involvement, haemorrhagic lesions, disseminated disease, ocular involvement, and cranial nerve involvement, or who have new and persistent symptoms after 6 days of oral medication should begin systemic therapy (Liang et al., 2016; Ojide et al., 2015).
Acyclovir has been combined with high-dose steroids to reduce the duration of acute zoster pain. Early studies indicated a minor effect of glucocorticoids on a few clinical outcomes, such as a better quality of life and faster lesion healing times (Gabutti et al., 2019; Hayward et al., 2018). However, a recent meta-analysis of five placebo-controlled trials comparing acyclovir + glucocorticoids to acyclovir alone did not show any benefits of combination therapy on post-herpetic neuralgia incidence or quality of life (Gabutti et al., 2019; Gaymard et al., 2018). The use of corticosteroids should also be carefully addressed, particularly in light of any potential side effects, such as an increased risk of secondary bacterial skin infection, inadequate glycaemic control, and a higher chance of cleft lip and palate in an embryo (Nanthakumar et al., 2021; Ojide et al., 2015). Only when a systemic antiviral medication is being used can corticosteroids be administered (Parente et al., 2018). Prednisolone (40 and 60 mg daily, with a dose reduction over 10–14 days to 5 mg daily) and acyclovir are the only medications for which study results are currently available (Sarma, 2020; Wutzler et al., 2021).
RQ3 was created to identify the following: What prophylactic practices are currently recommended in preventing and mitigating against varicella-zoster virus among pregnant women?
Findings from the identified studies showed contradicting findings of the prophylactic approach to VZV infection in pregnant women (Ibrahim et al., 2019; Krishnan & Sharma, 2020; Marin et al., 2014; Sauerbrei, 2016). The lack of common ground was attributed to the concerns that both varicella and zoster vaccines are contraindicated for women who are pregnant or may become pregnant within 30 days of receiving them, as is the case with other live-virus vaccines (Hanaoka et al., 2013; Ibrahim et al., 2019). The first dose of the vaccine for expectant women who are not immune to VZV should be given after delivery. To assure a lower risk throughout the following pregnancy and newborn protection through herd immunity, this vaccination approach is often done postpartum before discharge (Blumental & Lepage, 2019; Krishnan & Sharma, 2020).
To lessen the chance of spreading VZV to susceptible pregnant women, those with herpes zoster should cover lesions. Further, it is crucial to educate non-immune pregnant women to stay away from exposure to herpes zoster and varicella (Blumental & Lepage, 2019; Krishnan & Sharma, 2020; Shrim et al., 2018). Anti-VZV IgG antibodies should be checked right once if pregnant women exposed to varicella or herpes zoster have a negative or unclear history of varicella exposure (Marin et al., 2014; Ogbuanu et al., 2014; Pembrey et al., 2013). The patient should be considered susceptible if no antibodies can be found, the results are unclear, or the results are more than 96 hours late (Marin et al., 2014; Ogbuanu et al., 2014; Pembrey et al., 2013). Where it is delayed, indeterminate, negative, or unknown serologic status with confirmed high-risk exposure, pregnant women need to be given an intramuscular injection of VZIG within 72–96 hours.
However, insights from the identified literature show that there is no proof that VZIG prevents congenital varicella syndrome or foetal viremia, despite case reports that a passive immunisation could lower the risk of foetal infection (Pembrey et al., 2013; Shrim et al., 2018; Stephen & Gardella, 2014). VZ Ig is therefore primarily used to avoid severe maternal chickenpox and associated consequences. As such, it may be acceptable to infer that a pregnant woman is immune to varicella if she has a clear history of chickenpox. However, pregnant women who have received the varicella vaccine and who have negative VZV IgG tests should be treated as seronegative pregnant women (Sauerbrei, 2016; Shrim et al., 2018). Neonatal varicella-zoster immunoglobulin should be given whenever the commencement of maternal illness occurred five days before or two days after delivery (Benoit et al., 2015; Ibrahim et al., 2019; Krishnan & Sharma, 2020).

5.3. Discussion of the Research Process
Secondary data was largely used to inform the findings of this study. Essentially, the need to use secondary data to explore VZV in pregnant women was informed by its advantages. That is, undertaking a systematic review of past studies helps a researcher narrow the focus of the research problem and research questions (Ghauri et al., 2020). Systematic reviews also ensure there is a comprehensive search of evidence anchored on the criterion-based selection of suitable data and publications, thereby leading to rigorous appraisal of validity, objectivity, and evidence-based practices related to VZV infections, complications, optimal treatment, and prevention among pregnant women.
Insights from past studies show the growing use of secondary data to explore VZV infection, complications, and treatment (Ahn et al., 2016; Amjadi et al., 2017). The use of systematic studies and past publications on VZV is also time- and cost-effective compared to collecting primary data using interviews and surveys (Lau et al., 2020). In the process, the researcher is in a position to gain an understanding of the theory(ies) driving the field, making it possible to formulate research questions into suitable context. In this study, conducting a systematic review of VZV in pregnant women was key to finding relevant individual studies over varicella and herpes zoster during pregnancy, thereby making available evidence more accessible to care providers and public health practitioners regarding understanding complications, treatment, and vaccination.
The current systematic review provided a comprehensive summary of the current literature relevant to VZV during pregnancy while identifying remaining knowledge gaps that need to be filled in future research. That is, this systematic review is important not only to inform/guide decision-making and provide a synthesis of available evidence on a topic, but also to identify flaws, biases and gaps in knowledge, and to indicate in which direction it is worthwhile to prompt further research. Despite the strengths of using past publications to understand VZV infection in pregnant women, the current systematic research presents potential shortcomings that might affect the findings.
Potential limitations of systematic studies include risks of bias, such as selection bias, inadequate blinding for unavailability of data or subjective outcomes, attrition bias, selective outcome reporting, an inconsistency that includes statistical or clinical heterogeneity, and imprecision that can lead to Type I and Type II errors. Additional shortcomings include publication bias where positive clinical findings, reports or trials tend to be published more than negative reports (Swamy & Dotters, 2019). Also, there are concerns that statistically significant results may not always be clinically significant, thereby affecting the reliability of the systematic findings, especially for clinical providers. These limitations may have a potential impact on the research process and obtained findings due to subjective conclusions.
5.4. Public Health Relevance, Limitations, Conclusion, and Recommendations
Although chickenpox is a common childhood ailment, if it spreads during pregnancy, it is linked to major unfavourable sequelae such as congenital varicella syndrome, maternal VZV pneumonia, and newborn varicella infection, which can cause foetal a maternal morbidity and mortality. Although there is a VZV vaccine, it is neither generally advised for non-immune adult women in the UK nor is it currently part of the recommended paediatric immunisation schedules. Plans for handling exposure situations should be part of prevention measures. Antiviral medication, either by itself or in conjunction with VZIG, has been advised for the management of chickenpox in pregnancy.
Though the risk of mortality and morbidity from chickenpox is reduced by the use of antivirals, these outcomes are nevertheless possible. While VZIG lessens the frequency and severity of chickenpox, it does not eradicate it, and it is infective once symptoms are visible. Each obstetric unit should have a written protocol in place if a pregnant woman who has a history of contact with an index subject who has chickenpox visits a hospital public area or calls for advice. Such an approach will cut down on wasteful spending while providing the best protection for those who are most at risk for negative consequences. While herpes zoster can be concerning for a woman who is pregnant it also presents a health burden to society and public health. Therefore, the mother should be the primary recipient of care and therapy.
Acyclovir is safe for pregnant women because cohort and registry studies have found no relationship between acyclovir exposure and the risk of significant birth defects. However, acute illness treatment does not appreciably reduce the most prevalent long-term consequence, PHN. Pain management in pregnant patients can be challenging, but it should be a top priority. Physicians and patients must have a deeper understanding of herpes zoster and its complications to make informed decisions regarding herpes zoster treatment. Herpes zoster poses a risk of primary infection in persons who have not been exposed to or immunised against the varicella-zoster virus. Lastly, it is essential to note that the management of a pregnant zoster patient in an obstetric practice should ensure that additional women lacking immunity are not exposed to varicella.
The findings highlight important recommendations for public health practice including the following: (1) Vaccination against varicella is advised for all non-immune pregnant women as part of prenatal and postnatal care. (2) Vaccination against varicella should not be offered during pregnancy. Instead, vaccination administered inadvertently during pregnancy should not result in the recommendation of termination of pregnancy. (3) The antenatal varicella immune status of all pregnant women should be documented through a history of past infection, immunisation, or varicella-zoster IgG serology. (4) All non-immune pregnant women should be made aware of the risk of varicella infection for themselves and their unborn children. These women should be instructed to seek medical attention following any interaction with a potentially infected individual.
(5) In the case of a probable varicella exposure in a pregnant woman whose immune status is uncertain, serum testing should be conducted. If the serum findings are negative or cannot be obtained within 96 hours of exposure, varicella-zoster immunoglobulin should be provided. (6) All women who contract varicella during pregnancy need to be counselled and informed of the potential unfavourable maternal and foetal outcomes, the risk of transmission to the foetus, and the prenatal diagnosis methods available. (7) All pregnant women who have varicella are advised to get a thorough ultrasound and proper follow-up to screen for infection-related foetal effects. (8) Women with a substantial varicella infection (such as pneumonitis) during pregnancy need to be treated with oral antiviral medicines (including 800 mg acyclovir 5 times daily).
In situations of progression to varicella pneumonitis, maternal hospitalisation should be considered carefully. Consider intravenous acyclovir for severe pregnancy problems (oral forms have poor bioavailability). For varicella pneumonitis, the typical dose is 500 mg/m2 intravenous injection every 8 hours for 5-10 days, and treatment should begin within 24 to 72 hours of the commencement of rash. To improve early newborn care with varicella-zoster immunoglobulin and vaccination, neonatal health care practitioners need to be made aware of peripartum varicella exposure. Varicella-zoster immunoglobulin should be delivered to neonates if the onset of the mother’s sickness occurs between 5 and 2 days before delivery (Gaymard et al., 2018; Hayward et al., 2018).
5.5. Suggestions for Further Work
Suggestions for future research are informed by the potential shortcomings identified in the current study. Obtained findings show that there have been major advances in the treatment and prevention of herpes zoster and in managing PHN pain. However, the is still a persistent social and personal burden pregnant women are likely to experience. Thus, there is a need for further research about herpes zoster to eliminate diverse challenges and uncertainties which exist regarding complications, treatment, and prevention (Parente et al., 2018). Future research may focus on understanding how herpes zoster and varicella are likely to impact the epidemiological aspects of the ZVZ infection and its complications during pregnancy.
Future research may focus on shedding further information on potential risk factors for herpes zoster and its complications. Available knowledge shows controversy and lack of clarity on issues such as medical comorbidity, severity, nervous system senescence, and immune-senescence as potential risk factors (Nanthakumar et al., 2021). Moreover, there is a need to facilitate suitable methods for herpes zoster identification among pregnant women by care providers and patients and this could help initiation of timely treatment in women who are at higher risk for development of complications due to maternal varicella pneumonia. Such studies will help identify suitable methods to identify viral infection before rashes appear helping manage at-risk mothers with mild conditions.
The methods of acute pain and PHN also remain poorly understood (Sarma, 2020; Wutzler et al., 2021). Such challenges make it difficult to create an elaborate pain management plan. Further research on these challenges could help address existing uncertainties on how to improve pain management and promote quality of life among affected pregnant women. Additional studies on herpes zoster prevention, treatment, and prevention of its consequences, including are also required. These studies need to help identify more effective antiviral therapy among pregnant women, determine whether NSAIDs are effective, long-term prevention methods for PHN, ideally based on an improved understanding of pain mechanisms, and formulate new methods to stop VZV reactivation or to eradicate latent infection within neurons.

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