Congenital CMV infection and long-term sequelae 1. Neurogenic deafness (SNHL): SNHL is the most common and important of all sequelae caused by congenital CMV and can be the only manifestation of congenital CMV infection, and hearing loss can progress and worsen throughout childhood. SNHL occurs in 35-65% of symptomatic neonates with congenital CMV infection and in 7-15% of asymptomatic cases, and in 12% of congenital bilateral deafness caused by congenital CMV. Deafness caused by CMV infection is not evident in the neonatal period, but progresses gradually during childhood. In a study of newborns with asymptomatic congenital CMV infection, SNHL was found to occur in 7.2%, half of whom had worsening hearing impairment. Their median age was 18 months. Late onset SNHL occurred in 18.2%, with a median age of 27 months. Newborns with congenital CMV infection should be monitored throughout childhood for early detection of SNHL, and newborn hearing screening can detect SNHL due to congenital CMV infection in less than half of cases. Because SNHL is progressive, hearing screening should be combined with CMV screening. When newborns have evidence of CMV infection and a normal hearing screen, these children should be monitored for evidence of SNHL throughout childhood. Viral inclusion bodies can invade the endolymphatic and ectolymphatic fluid of the vagus during viremia, causing degeneration and loss of internal and external hair cells but the mechanism is unknown. It is possible that CMV infects hair cells directly and causes their loss, and can also cause hair cell damage and inner ear damage at the time and later through the inflammatory response of the inner ear. In addition, the occurrence of SHNL is associated with host genetic susceptibility to CMV. Most newborns with congenital CMV infection are asymptomatic at birth, but 15% have sensory hearing loss by 72 months postnatally. In addition viral load is associated with SNHL, and those who develop SNHL have a higher viral load. When the viral load is < 1000 copies per 105 polymorphonuclear leukocytes, SNHL is less likely to occur. 2. CMV and epilepsy: In infants with neonatal CMV infection, neurological sequelae occur in 90% of those with symptoms and 10-15% of those without symptoms. The main ones are mental retardation, cerebral palsy, visual impairment, and convulsions, but the relationship between CMV infection and epilepsy has been little studied because it is generally described as convulsions. A Japanese study on congenital CMV infection and epilepsy found that among 19 children with congenital CMV infection, a total of 7 cases developed epilepsy, of which 6/16 (38%) were symptomatic CMV infections and 1/3 (33%) were asymptomatic children. There was no difference in epileptogenesis between the two groups. 3 cases developed within 1 year of age and 4 cases developed between 1 and 4 years of age, with a mean age of onset of 20 months. Seizure types: infantile spasms in 3 cases, partial seizures in 3 cases, and partial seizures with generalized tonic clonic seizures in 2 cases. Parental misconceptions Once an infant is diagnosed with CMV infection or CMV hepatitis parents find it unbelievable. Many mothers think that how can they be infected with CMV when everything was normal during pregnancy? Other mothers think that they have been tested for CMV antibodies during pregnancy and have confirmed that they do not have any viral infection, so how can their child have CMV? This is because most adults with CMV infection have no symptoms, and if they do, they are mild and cannot be easily distinguished from the flu. In addition, the virological tests given to pregnant women in obstetrics are usually done in the early stages of pregnancy, mostly in the first 3 months of pregnancy. However, just because a pregnant woman is confirmed to be free of infection in the first trimester does not mean that she is free of infection throughout her pregnancy. Infected fetuses in early pregnancy are prone to miscarriage and malformations, while infections in late pregnancy may not only be asymptomatic, but may also result in newborns with no abnormalities or only unexplained hyperbilirubinemia. Treatment of CMV infected infants can be detoxified for months or even years, so it is important to isolate pregnant women to prevent them from being infected. The disease is difficult to treat and currently the main drug used to treat CMV infection in China is ganciclovir. Ganciclovir GCV is a broad-spectrum anti-herpes virus drug that is effective against CMV, and is the first synthetic drug approved by the FDA to treat CMV retinitis and prevent CMV infection after organ transplantation. Intravenous GCV 5mg/kg. times is sufficient to inhibit CMV in subretinal fluid, cerebrospinal fluid, and brain tissue. most of GCV is excreted through urine with a clearance half-life of 2-3 hours, and the dose needs to be reduced in patients with impaired renal function. The pharmacokinetics in neonates are similar to those in adults. The protection against hearing impairment in neonates can last for more than one year with intravenous 6 mg/kg twice daily for 6 weeks. The bioavailability of oral ganciclovir is very low, with less than 10% absorption. The main side effects of GCV are myelosuppression and dose-related granulocytopenia, which occurs in 40% and is reversible with discontinuation of the drug. 20% of patients develop thrombocytopenia (≤50,000) and 2% have anemia. A small number of patients experienced headache, confusion, hallucinations, nightmares, anxiety, ataxia, convulsions, fever, rash, abnormal blood liver enzymes, and renal impairment. GCV has also been shown to be mutagenic, carcinogenic, and teratogenic in preclinical animal studies. However, they have not been confirmed in humans. Ganciclovir is cleared by the kidneys, so the dose should be reduced in the presence of renal insufficiency. Resistance in treatment may occur, but there are no reports of treatment of neonatal congenital CMV infection with GCV resulting in drug resistance. Because GCV is only available in intravenous formulations and is administered twice daily, it is difficult for parents of children to adhere to long-term therapy. The oral formulation, called valganciclovir, is a single valacyclovir precursor drug for GCV, which is quickly converted to GCV after oral absorption, and was approved by the FDA in 2000 for the treatment of CMV retinitis in AIDS patients combined with CMV, and later approved for the prevention of CMV in solid organ transplant recipients. pharmacogenetic studies of oral valganciclovir syrup have been completed in neonates. However, this drug is not yet available in China, and it is hoped that it will be introduced in our country in the near future. Other anti-CMV drugs include phosphonate and cidofovir, but they are rarely used in neonates because of their side effects. Treatment experience: Six weeks of intravenous GCV treatment for symptomatic congenital CMV infection improved auditory evoked potentials at six months, and for those with normal hearing at enrollment, normal hearing was maintained at six months. 84% of those with GCV had improved or maintained normal hearing at six months, while only 59% of the control group had improved or stabilized. Forty-three children had brainstem auditory evoked potentials before and at 12 months of treatment, and it was found that 21% of the GCV-treated group and 68% of the control group had worsened hearing impairment. There is no uniform treatment protocol for GCV treatment at home and abroad, but many foreign studies on the treatment of neonatal CMV infection have used a regimen of 6 mg per kg body weight per day for 6 weeks for clinical efficacy and prognosis. Most of the treatment targets are symptomatic CMV-infected patients. Current treatment status and treatment recommendations in China The indications and treatment methods for the treatment of congenital CMV infection in China are still confusing, some indications are too broad, for example, some doctors start treatment as soon as CMV IgM antibody is positive or CMV DNA is detected in urine, and most use a two-week regimen, but the recurrence rate is high. Therefore, it is recommended that asymptomatic infants with confirmed CMV infection be monitored for liver function, neurodevelopment, and regular hearing examinations without immediate treatment with GCV, and that treatment be considered only when signs and symptoms of CMV infection are present. For example, treatment should only be considered if the infant has hepatitis, hearing impairment, or neurodevelopmental abnormalities, and parents should be informed of the side effects and possible hazards of the medication and should make a careful decision. Once the decision is made to treat with antiviral therapy try to adhere to the treatment for 4-6 weeks, otherwise there may be a relapse after stopping the medication.