TORCH is a combination of T for toxoplasmosis (TOX), O for other, mainly syphilis in pregnancy, R for rubella virus (RV), C for cytomegalovirus (CMV), and H for herpes simplex virus (HSV). TORCH infections in pregnant women have mild or even no obvious signs and symptoms, but all of these pathogens can cause fetuses and newborns to exhibit severe signs and symptoms, and can leave behind central nervous system damage or even death. The pharmacological treatment of TORCH infection in pregnant women is introduced according to the 5 grading criteria of drug risk to pregnancy issued by FDA.
1. Drug treatment of toxoplasmosis in pregnancy
Toxoplasmosis is a zoonotic parasitic disease. The symptoms of Toxoplasma gondii infection in pregnant women are mild, and the symptoms are not obvious in most cases. However, it can cause congenital toxoplasmosis in the fetus, which mainly manifests as retinal chorioretinitis, ventricular calcification and hydrocephalus. The rate of fetal infection is related to whether the mother is first infected and the week of gestation at the time of infection. The fetal infection rate is 17%, 25% and 65% when the mother is first infected in early, middle and late pregnancy, respectively. Re-infection of the fetus with Toxoplasma gondii usually has no effect on the fetus.
The transmission of maternal infection to the fetus is usually limited to one fetus, with some exceptions. Once Toxoplasma gondii infection is detected during pregnancy, it should be treated actively. The earlier the treatment, the less the sequelae of the baby will appear. At present, the main drugs used to treat Toxoplasma gondii infection are ethacridine, cotrimoxazole (cotrimoxazole) and acetylspiramycin.
(1) Ethamiprazine, classified as Class C by FDA. Ethacil is an inhibitor of dihydrofolate reductase and is often used in combination with sulfadiazine to treat toxoplasmosis. Animal experiments have found teratogenic effects of pyrimethamine. It is generally believed that drugs that inhibit folate metabolism (e.g. methotrexate) may be teratogenic for humans. However, there is no data to prove the teratogenic effect of ethacrynic acid on the fetus. In view of its ability to inhibit folic acid metabolism, it is advisable to use it with caution during pregnancy, especially in early pregnancy, and to supplement folic acid when necessary. Ethacrynic pyrimidine can be introduced into breast milk, but the American Academy of Pediatrics considers the use of this product during lactation to be acceptable for breastfeeding. Ethamiprazine should be given as 50 mg orally in 2 divided doses daily and changed to 25 mg once daily after 2 days for 1 month. Because ethamethazine may suppress bone marrow, review blood picture at least once a week during treatment. Total white blood cell count less than 3.0×109/L and platelet count less than 100×109/L should be discontinued promptly.
(2) Compound sulfamethoxazole is a compound of sulfamethoxazole and meperidine, which is classified as Class C by FDA. Sulfamethoxazole can pass through the placenta, and animal tests have found that malformations occur in pregnant rats after taking large amounts of sulfamethoxazole. Sulfamethoxazole has been shown to increase mortality in pregnant rabbits, but no malformations have been observed in rabbits. In humans, there is no sufficient information to prove the teratogenicity of this product. Methotrexate can also pass through the placenta. Animal experiments have demonstrated that methotrexate has teratogenic effects, mainly cleft lip and cleft palate.
It has been reported in the literature that the incidence of neonatal malformations was 5.5% with cardiovascular malformations being more common when methotrexate was used in early pregnancy. Compound sulfamethoxazole should not be used in early pregnancy because of the interference of methotrexate with folic acid metabolism. Sulfamethoxazole can be introduced into breast milk. Maternal breastfeeding is not recommended, especially for premature infants, infants with hyperbilirubinemia or glucose-6-phosphate dehydrogenase deficiency, and breastfeeding should be prohibited. Sulfamethoxazole: 2 tablets twice daily (each tablet contains 400mg of sulfamethoxazole and 80mg of meperidine).
(3) Acetylspiramycin, classified as Class C by FDA. After taking this product, the concentration in the placenta and other tissues is high, and it is basically harmless to the fetus. It is suitable for pregnant women with toxoplasmosis. It can pass through the placenta. After oral administration, the drug concentration ratio of umbilical cord blood/maternal blood is about 0.5, while the drug concentration in placental tissue is 2-4 times higher than that in maternal blood. This product is widely used in western countries and no adverse effects on fetus have been observed. Acetylspiramycin can be introduced into breast milk; use this product with caution during lactation. Acetylspiramycin usage: 0.2 each time, 4 times daily, 3 weeks as a course of treatment, after 1 week of discontinuation, can be repeated.
2. Drug treatment of syphilis in pregnancy
Syphilis is a sexually transmitted disease caused by syphilis spirochetes. In the early stage, it mainly invades the skin and mucous membrane, and in the late stage, it invades the cardiovascular system and central nervous system. Many pregnant women may have no history, no localized lesions or rash until the delivery of a stillborn baby or a premature baby with severe congenital syphilis is detected.
Treatment of syphilis in pregnancy has a dual purpose: to treat the pregnant woman and to prevent or reduce the occurrence of congenital syphilis. The treatment of syphilis with penicillin is preferred and should be used early, in sufficient quantity and regularly. Tetracycline or erythromycin is used for those who are allergic to penicillin.
(1) Benzathine penicillin is classified as Class C by FDA. It is long-acting penicillin. Benzathine penicillin can rapidly enter the blood and amniotic fluid of the fetus through the placenta. A large number of clinical practice has proved that it is not teratogenic to the fetus. The data from the National Perinatal Collaborative Program in the United States showed that no teratogenic effects on the fetus were found in more than 3000 pregnant women who used penicillin in early pregnancy. However, during the treatment of syphilis, as a large number of syphilis spirochetes are killed, a large number of heterotypic proteins are produced and released into the patient’s bloodstream, which can result in uterine contractions, abnormal fetal heart rate, intrauterine fetal death and stillbirth. Usage: Benzathine penicillin 2.4 million units intramuscular injection once a week for 3 times.
(2) Tetracycline FDA classified as Class D. This product can enter the fetal circulation and amniotic fluid through the placenta. Animal experiments have shown that the use of this product in early pregnancy has embryotoxic effects, but in humans it has not been proven to have embryotoxic effects. It has been reported in the literature that the use of this product after 5 months of gestation in pregnant women may cause yellowing of teeth, underdevelopment of tooth enamel and delayed bone growth in infants. In addition, tetracycline is toxic to the liver of pregnant women and can cause serious complications such as acute fatty liver degeneration in pregnant women. It is now generally accepted that tetracycline is contraindicated during pregnancy.
One possible indication for the application of tetracycline in pregnancy is a pregnant woman with syphilis infection, who is allergic to penicillin and cannot be desensitized.
(3) Erythromycin is classified as Class B by the FDA. There is no information to prove the teratogenic effect of this product. There is information that more than 6,000 pregnant women who used this product in early pregnancy were not found to have significant teratogenic effects on the fetus. Erythromycin has greater hepatotoxicity and should be avoided as much as possible. Although this product can enter the fetal circulation through the placenta, the amount is very small, so it cannot play a role in the prevention and treatment of fetal syphilis. Dosage: 500mg per dose, 4 times daily for 15 days.
3.Treatment of rubella in pregnancy
Rubella is an acute viral infection transmitted through the respiratory tract, with mild clinical symptoms and a good prognosis, which can easily be ignored. However, rubella virus can infect the embryo or fetus in the womb via the placenta and cause congenital rubella syndrome. There are three main features: cardiovascular malformations, congenital cataracts and congenital deafness. The earlier the gestation period, the greater the chance of infecting the fetus. Fetal involvement is 50% in the first month of pregnancy, 30% in the second month of pregnancy, 20% in the third month of pregnancy, and less than 5% after the fourth month of pregnancy.
Rubella reinfection can also cause congenital rubella syndrome, but is very rare. Although rubella reinfection can be isolated from the pharynx, it is transient, the amount of virus is small, and viremia does not usually develop. Therefore, intrauterine infections are rare.
There is no specific drug treatment for rubella virus. Pregnant women with rubella need to be more careful with medications and be aware of the effects on the fetus. The first infection with rubella virus confirmed in early pregnancy should be considered for termination of pregnancy by abortion. If you are infected with rubella virus in the middle or late stages of pregnancy, intrauterine diagnosis should be done in order to rule out the possibility of fetal rubella virus infection.
4. Drug treatment of cytomegalovirus infection in pregnancy
Cytomegalovirus infection is a human infectious disease caused by cytomegalovirus, and close contact with a detoxified person is the main mode of transmission of cytomegalovirus infection acquired later in life. Primary infection with cytomegalovirus in pregnant women transmits the virus vertically to the fetus in about 40% of cases, which is extremely harmful to the fetus and is one of the most important pathogens causing congenital defects and mental retardation in newborns. In contrast, the risk of disease in infants with recurrent cytomegalovirus infection in pregnant women is extremely low. The majority of cytomegalovirus infections in pregnant women are subclinical and generally do not require specific treatment.
Even if intrauterine cytomegalovirus infection is detected by prenatal diagnosis, drug treatment is not advocated because it does not improve the prognosis of the newborn. Antiviral therapy should only be considered if the pregnant woman is immunocompromised and has symptoms of overt cytomegalovirus infection. The drug currently considered more effective is ganciclovir.
Ganciclovir, classified as Class C by the FDA. This drug has significantly greater in vitro inhibitory effect on human herpes viruses than acyclovir. It is indicated for herpes virus infections in addition to cytomegalovirus infections in AIDS and other immunocompromised patients. Animal studies have found embryotoxic and teratogenic effects on rodents. No studies have been conducted to confirm the safety of this product for the fetus in pregnant women.
This product should not be used in pregnant women without special needs. This product should not be used in breastfeeding women, and if indicated, breastfeeding should be stopped.
5. Drug treatment of herpes simplex virus infection in pregnancy
Herpes simplex virus infection is the most common viral disease in humans. HSV-1 mostly causes herpes of the skin above the waist and herpes of the eyes and mouth, while HSV-11 mostly causes herpes of the skin below the waist and external genital herpes. Herpes simplex virus is widespread in the population, and humans are the only hosts and patients and carriers are the only sources of infection.
Women with the disease in early and middle pregnancy have rare fetal infections during pregnancy, and even in late pregnancy, patients whose serology turns positive (indicating the development of antibodies) before delivery rarely have newborns with the disease. Therefore, only pregnant women who become ill within a short period of time before delivery may transmit the virus to their newborns because they do not have antibodies. However, once a newborn is infected with the herpes simplex virus, the prognosis is very poor. Approximately half of all newborns die, and most of the other half will have central nervous system sequelae.
Prophylactic use of acyclovir in late pregnancy has been reported in the literature to potentially reduce recurrent herpes simplex virus infection and thus reduce cesarean delivery rates.
Acyclovir, classified as Class C by the FDA. Its anti-herpesvirus activity is 150 times stronger than that of acecloadenosine. Its application to pregnant rats can affect thymus development and cause defects in immune system function. Chromosome breakage can occur when high concentrations of acyclovir are added to human lymphocytes in culture. Acyclovir crosses the placenta with a cord blood/maternal blood concentration ratio of 1.25-1.4. In 478 cases of early pregnancy, no significant teratogenic effects were observed.
In early pregnancy, acyclovir is generally not recommended unless systemic diffuse herpesvirus infection has occurred. In contrast, oral acyclovir in late pregnancy is more economical than cesarean delivery to prevent herpesvirus infection in the newborn. Acyclovir is administered as 0.2 g 5 times daily for 2-4 weeks.