䡵Vaccination

Management of Viral Infection
during Pregnancy
JMAJ 45(2): 69–74, 2002

Takashi KAWANA

Professor of Obstetrics and Gynecology, Teikyo University Mizonokuchi Hospital

Abstract: Viral infection during pregnancy should be handled from two main
aspects, maternal management and the prevention of mother-to-child transmis-
sion. Infectious diseases in pregnant women are likely to become severe because
cellular immunity is suppressed during pregnancy. Therefore, careful management
is necessary in this population. The virus infecting the mother’s body may be
transmitted to the fetus or neonate through the following three routes: intrauterine
transmission, intrapartum transmission, and transmission via breast milk. It is
difficult to prevent intrauterine transmission, and therefore preventing maternal
infection is prudent. Since the rubella vaccination rate has been decreasing
recently, there is concern that the prevalence of antibody among pregnant women
may decline as well. Maternal varicella infection in early pregnancy is said to result
in congenital varicella syndrome in about 2% of infants born to infected mothers.
About 10% of pregnant women who have been infected with human parvovirus B19
in early pregnancy reportedly experience miscarriage, and some of them are
associated with fetal hydrops. Mother-to-child transmission of hepatitis B virus can
be prevented in more than 90% of cases through the use of HBIG and HB vaccine.
Mother-to-child transmission of viral infectious diseases is responsible not only for
fetal or neonatal diseases but also for adult diseases. Therefore, collaborative
studies involving the fields of obstetrics and gynecology, pediatrics, internal medi-
cine, ophthalmology, and otolaryngology are required.
Key words: Mother-to-child transmission; TORCH syndrome;
Preventive vaccination

cooperation, and refers to new developments
Introduction
in the area of TORCH syndrome. TORCH is
This paper discusses viral infection and mater- an acronym coined in the 1970s from the names
nal and child management in connection with of various infectious diseases that can lead to
the themes of pregnancy and interdisciplinary abnormal child birth if the mother is infected

This article is a revised English version of a paper originally published in
the Journal of the Japan Medical Association (Vol. 124, No. 7, 2000, pages 1013–1016).

JMAJ, February 2002—Vol. 45, No. 2 69

among them var. the manage. and time of mother-to-child transmission. two issues are of concern. C for cyto. cirrhosis. R for rubella.T. February 2002—Vol. Adult T cell leukemia virus can also produce Hepatitis B virus Chronic hepatitis. liver cancer carriers via mother-to-child transmission. retinitis become adults. mission (transmission in the birth canal). but the presence of for other (syphilis). ment of infected pregnant women and the pos. of mother-to-child transmission is necessary. Intrapartum transmis- natal infection. 2 . with maternal blood in the parturient canal or infants who become carriers of the hepatitis B when the maternal blood is transferred to the 70 JMAJ. sion may occur when the fetus comes in contact eases that manifest in adulthood. ophthalmic. which are particular problems in cases has invaded the mother’s body. mitted during delivery. it is necessary to know the route adult T cell leukemia virus. KAWANA Table 1 Infectious Diseases in Children and Adults virus through mother-to-child transmission Occurring Through Mother-to-child Transmission may develop chronic hepatitis. difficult to prevent intrauterine transmission. For example. premature hepatitis B virus infection are generally trans- delivery. In a wide spectrum of abnormalities and illnesses contrast. medical. management focused on the prevention mother-to-child transmission. with drugs that might otherwise Subsequently. hepatitis B virus. and HTLV-1 Adult T-cell leukemia these infants develop leukemia when they Cytomegalovirus Hearing loss. parvovirus B19. stillbirth. attention was given to a number be used routinely administered with caution. intrapartum transmission can be prevented by sibility of pediatric. Mother- matis. Syphilis Keratitis. herpes simplex virus infection and ranging from miscarriage. although not all cases of mother-to-child transmission can be classified Transmission into these three categories in such a clear-cut When the immunologically immature fetus manner. and H for herpes simplex virus. dental abnormality Management of Infectious Diseases in Pregnant Women First of all. Because of to-child transmission can occur in three ways: space limitations. and cesarean section and transmission via breast otolaryngologic diseases of children infected milk by avoiding breast feeding. of primary infection occurring during early preg- quences may result. various conse. No. and group B streptococci. Chlamydia tracho. of pathogens that affect the fetus through Next. For icella virus. thyroiditis mitted from mother to child as a possible route HIV Pediatric AIDS are shown in Table 1. Although it is often eration. transmission via breast milk. through mother-to-child transmission. congenital infection. Rubella virus infection and toxoplasma or newborn is infected with a pathogen that infection. this purpose. and infantile infection to dis. the fetus should always be borne in mind during megalovirus. Table 2 shows the classifications of routes of major infectious diseases involving mother-to- Consequences of Mother-to-child child transmission. the disease of the pregnant woman during pregnancy: T stands for toxoplasma. neo. deformity. Diseases in children and adults Toxoplasma Retinitis Varicella-zoster virus Pediatric zoster currently known to be caused by agents trans- Rubella virus Diabetes mellitus. O herself should be treated. this paper will focus on viruses intrauterine transmission. and From the standpoint of interdisciplinary coop. hearing loss. intrapartum trans- and toxoplasma. are generally transmitted in utero. 45. such treatment. resulting in cir- Etiologic agent Disease rhosis and hepatic carcinoma 30–40 years later. These consequences include nancy.

February 2002—Vol. VIRAL INFECTION DURING PREGNANCY Table 2 Major Infectious Diseases in Japan Mediated by Mother-to-child Transmission and Their Routes of Transmission Intrapartum transmission Intrauterine (transmission in the Transmission transmission parturient canal) via breast milk Viruses Rubella virus A⬘ E(?) E Cytomegalovirus A⬘ A(?) A Parvovirus B19 A⬘ E(?) E Varicella-zoster virus B⬘ A(?) E Herpes simplex virus B⬘ A(?) E Coxsackievirus C⬘ E(?) E Hepatitis B virus D⬘ A(?) E Hepatitis C virus D⬘ B(?) E ATL virus D⬘ D(?) A AIDS virus D⬘ A(?) B Chlamydia Chlamydia trachomatis E⬘ A(?) E Bacteria Syphilis A⬘ A(?) E Gonococci E⬘ A(?) E Group B hemolytic streptococci E⬘ A(?) E Fungus Candida albicans E⬘ A(?) E Protozoon Toxoplasma A⬘ E(?) E *Importance is graded from A to E (A denotes highest importance). This route is cesarean section to prevent transmission in the important for the mother-to-child transmission parturient canal and avoidance of breast feed- of hepatitis B virus and HIV infections because ing to prevent transmission via breast milk. vention. Reduction of the amount of HIV in HIV-carrying mothers by antiviral drug ther. infection of the mother should be and children born to mothers who have had prevented. infected child preemptive therapy. prevention. The the pathogens are present in the maternal blood. In the stage of primary B virus will be given HBIG and HB vaccine. For instance. Rubella virus apy is an example. 45. mother-to-child transmission should be prevented by implementing treatment of the Individual Diseases infected mother. For instance. No. lin (VZIG). the author has divided the prac. women who want to varicella during the perinatal period will be conceive should have established immunity to given high-titer varicella-zoster immune globu- rubella in advance. 2 71 . tical prevention of mother-to-child transmis. children born to mothers who carry hepatitis sion into four stages. fetus as a result of labor pains. Tertiary prevention involves It is well known that 30–50% of pregnant JMAJ. 1. In the second stage of pre. final stage of prevention involves the inhibition Taking into consideration these mechanisms of clinical manifestations of disease in the of transmission.

it is most efficient to establish immu. No.8% (4/477) (13–24 weeks) 21–36 weeks 0. and it is among children. early implementa- year of junior high school gave way to immuni. An include scarring of the skin. should be expanded nationwide. Since CRS is virus (VZV) seems to be approximately 90% widespread in years when rubella is common among individuals in their 20s and 30s.0% (0/366) (Enders. The incidence of fetal abnormality is immunization to voluntary immunization has reportedly 0% if the mother develops herpes caused the vaccination rate among junior high zoster. are con. and hypoplasia of the extremities. that the incidence of such abnormalities is 0. Labor and Welfare through mother-to-child transmission of the (JMA News. together with until 12 weeks of gestation. This problem may be enhanced varicella patient.4% sidered to have been eliminated. No infants eliminated.0% (0/475) 1. May 5 2000 issue). the change from scheduled mass tation. of gestation. Rubella vaccination has been pro.1) taneously. neonatal varicella may develop the Ministry of Health.T.0% (0/97) 0. Abnormalities occurring in the fetus school students to fall to less than 50%. et al. tion of intravenous drip infusion of aciclovir is zation on a voluntary basis in infants up to 90 recommended. If immunization with rubella vaccine in the second signs of pneumonia appear. which A large-scale German and British study revealed have tended to occur every 5–6 years. this procedure. nancy deliver infants with congenital rubella syn- drome (CRS). months old and male and female junior high It has become apparent that abnormalities school students. epidemics of rubella. varicella. with nancy may be severe and is often complicated the new revision. Varicella-zoster virus with CRS. providing less chance for these with abnormalities have been born to mothers seronegative individuals to catch rubella spon. it is important to suppress not uncommon for pregnant women to develop epidemics of rubella. To prevent the birth of infants 2. 45.0% at 13–20 weeks a probable decrease in the incidence of CRS. the previous pre. With the implementation of may occur in the fetus if the mother has varicella. 2. ophthalmic abnor- increased proportion of seronegative individu. malities. February 2002—Vol. and. and 0% after 21 weeks of ges- However.0% (6/345) (25–36 weeks) exposure Zoster 0. prevention of infection is by the fact that epidemics of rubella have been attempted by administering VZIG. Since varicella occurring during preg- ventive vaccination law was revised. due caution is necessary. If infection with VZV takes place during 72 JMAJ.7% (6/345) (25–36 weeks) VZIG therapy after 0.0% (7/351) 0. KAWANA Table 3 Time of Infection of the Mother with Varicella and Effects on the Fetus Incidence of congenital Time of infection varicella syndrome Infantile zoster Varicella 0–12 weeks 0. who received such treatment (Table 3). If als may be an issue when such individuals reach a pregnant woman comes in contact with a reproductive age. These efforts virus. The prevalence of antibody to varicella-zoster nity in women before pregnancy. In 1994. 2 . the earlier procedure of mass by pneumonia.4% (2/472) 13–20 weeks 2. G. If the mother is infected with varicella at the moted by the Japan Medical Association and time of delivery.: Lancet 1994) women infected with rubella during early preg.

At first. VIRAL INFECTION DURING PREGNANCY the period from 4 days before to 2 days after among infants born to HB virus carriers who delivery.300 per year the onset of labor pains may be inhibited to to 420 per year. varicella in neonates is likely to be are negative for HBe antigen. contraindication because of the possibility of gen-positive mothers were given HBIG imme. infants carrying HB virus. No vaccine against this sion are preventable by abdominal delivery by virus is currently available. This project just after birth. cesarean section if herpetic lesions are found in nant women may be mediated by their own the external genitalia or cervical canal of the children who have become infected in day care uterus. It has been more than 15 years since preven- tive measures were first taken on a national Vaccination basis in response to the finding that the inci- dence of mother-to-child transmission is high Vaccination is contraindicated during preg- among infants born to mothers who are HBV nancy. More virus. confirming the benefits 3. been reported of CRS infants born to high-risk ent that the incidence of infection is about 10% mothers who received vaccination in the early JMAJ. A finding women.2) mission of HSV is extremely rare. fortunately. if there are only almost nil. and aciclovir therapy should be resulted in a marked decrease in the number of given as needed. as in recurrent cases. does not appear to occur at a significantly ity of fetal deformity as a result of intrauterine higher rate in infants born to mothers who have transmission of parvovirus B19 is considered received this drug. slight signs and symptoms. but some- VZIG should be administered to the neonate what simplified preventive measures. by which time IgG anti. 45. 2 73 . of particular interest was that fetal hydrops Fetal anomaly caused by the intrauterine trans- may occur. and it soon became apparent that 5. and about 10% suffer miscarriage or than 95% of cases of mother-to-child transmis- premature delivery. It was determined that parvovirus B19 causes this disease. No. frequently resulting in stillbirth. transmission to the fetus. two months after the inoculation of rubella because such infants are infected with HBV at a vaccine. and this group of particularly frequent and severe. Live vaccine in particular is an absolute carriers.3) This is work in pediatric departments to be infected via grounded on the recent finding that deformity young children in the workplace. February 2002—Vol. topical application of an ointment containing 4. the onset of varicella. However. Although the long-term ben- allow birth to take place 7 or more days after efits of this procedure initially were questioned. However. It should be kept diately and 2 months after birth. Infection in preg. infants was also subjected to similar. Hepatitis B virus (HBV) anti-herpes virus is sufficient treatment. It is also common for pregnant women with aciclovir is feasible for the treatment of who work in day care centers or nurses who genital herpes in pregnant women. It often takes the form of genital herpes. only infants born to HBe anti. it has become apparent that children who under- body production begins in the maternal body. Later. followed by in mind that contraception is necessary for three inoculations of HB vaccine thereafter. from 3. it became appar. From the obstetric viewpoint. The possibil. In this case. Erythema infectiosum (fifth disease) of the procedure. It has been advocated that medication centers. no cases have rate of more than 90%. Herpes simplex virus (HSV) intrauterine transmission of the virus might cause HSV infection is not uncommon in pregnant miscarriage and premature delivery. went these preventive measures are still sero- negative after 10 years. A greater Intrauterine transmission is considered to occur problem is the development of neonatal herpes in about 30% of mothers infected with this caused by transmission in the birth canal.

Lancet 1994. Increases in the incidence of nervous system was previously suggested. and toxo- a general rule that inactivated vaccine should plasma.. this relationship is currently denied. T. Consequence of varicella and herpes zoster in pregnancy: Prospective study of 1739 cases. vaccination. 45. If this is true. and hence there appears to be no need 1) Enders. collaborative research by pediatricians. G. 343: 1547–1550.: for vaccination. February 2002—Vol. A.. it is megalovirus. in light of the results of such studies. 316: 183–186. for efficient strategies against rubella virus. active use of vaccination should be con- REFERENCES sidered. 47(No. child transmission are needed. vaccine when influenza is widely prevalent. E. however.: Human parvovirus infection in pregnancy and hydrops The consequences of mother-to-child trans- fetalis. et al. No. It is a difficult placental route and lead to the birth of abnor- problem as to whether or not pregnant women mal infants even when infected mothers do not should be inoculated with inactivated influenza show any clinical signs and symptoms. it is currently thought to be unlikely. In theory. KAWANA pregnancy period or who conceived soon after thalmologists. all of which are transmissible via trans- not be given to pregnant women. I. (CDC): 1998 guidelines for treatment of sexu- Prospective studies of children after mother-to.S. et al. particularly as RR-1): 25–26. Gray. E.. monia would be high in pregnant women. It was ant increases in the incidence of fetal and neo- also reported that mortality from influenza pneu. otolaryngologists. MMWR 1998. mission involve not only fetuses and neonates 3) Centers for Disease Control and Prevention but also extend to older children and adults. Cradoke-Watson. Miller. oph- 74 JMAJ. and internists. a pregnant women has recently been reported relationship with abnormalities of the central for some viruses. N Engl J Med 1987. However. Brown.T. natal anomalies are of recent concern. How. vaccine made from inactivated The search is underway in the obstetric field virus has no effect on the fetus and. primary infection in pregnant women and result- ever. herpes simplex virus. In The decreased prevalence of antibody among regard to the teratogenicity of influenza virus. cyto- can be used in pregnant women. 2 .. ally transmitted diseases. Conclusion 2) Amand. therefore. It seems that attenuated rubella Obstetric management should be reconsidered virus used for vaccination is less teratogenic.