September 1999
HOUSTON, Texas - Vaccinating pregnant women may provide protection against potentially fatal infections for infants in a safe and practical way and provide protection for the mother as well.
Tetanus toxoid and influenza vaccines are already known to provide double benefit. Vaccines for adults targeted against respiratory syncytial virus (RSV), pneumococci, group B streptococci (GBS) and Haemophilus influenzaetype b (Hib) are currently under evaluation. Maternal immunization with these vaccines could potentially save millions of lives and attack diseases in an efficient manner.
Most IgG antibody crosses the placenta in the third trimester; however immunization ideally should occur at least six weeks before delivery. Maternal immunization has not interfered with infant active immunization, and available data suggest that inactivated vaccines given in the third trimester do not pose any risks to mother or baby.
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RSV is one of the most common illnesses affecting infants, with the highest rate of hospitalization occurring at 2 months of age, before effective immunization can occur. High levels of maternal antibody can lessen the severity of RSV in young infants. Maternal antibody should decrease the risk of serious respiratory tract disease, as well as infant hospitalizations. Seventy-five percent of infants hospitalized with RSV-associated lower respiratory tract infections are younger than 5 months, so maternal immunization with RSV subunit vaccine may prevent many early infancy lower respiratory tract infections.
Currently it is believed that women may need to be immunized against RSV every time they become pregnant, due to falling titers after a few months. The vaccine would be recommended on a similar schedule as influenza.
"Women who are going to deliver during RSV season really should have their titers boosted," said William P. Glezen, MD, Baylor College of Medicine, Houston, Texas.
An infant's level of protection against RSV depends greatly upon when the mother is immunized. "We are hoping to increase protection for at least the first four months," Glezen said. "The younger the baby at the time of infection, the worse the disease is. Babies who get infected in the first few months of life have greater risk of severe disease. The older they are when they get infected, the less severe the disease. So the time the antibody is present correlates to when they need it most."
Pneumococci are strongly associated with acute otitis media, meningitis and pneumonia. Worldwide, each year, pneumococcal pneumonia is responsible for more than 1 million deaths of children younger than 5, but infections occurring in early infancy have the greatest risk of death. Most infants do not have sufficient antibody response to polysaccharide antigens, so boosting maternal titers may be beneficial. Serum antibody passed through maternal immunization and breast milk antibody could significantly reduce serious infections in a child's first month of life, Glezen said.
The currently approved Streptococcus pneumoniae polysaccharide vaccines are recommended for women with high-risk pregnancies, such as a mother who is missing a spleen or has sickle cell disease and has not had a recent pneumococcal vaccine dose. Studies are planned for healthy pregnant women to see if maternal vaccination will reduce otitis media cases in the first six months of life.
Fulminating sepsis in the neonatal period is most frequently caused by GBS, a common cause of bacteremia and meningitis in the first two months of life. The maternal genital tract is usually the source of infection.
Pregnant women may suffer from chorioamnionitis or urinary tract infection, which can preclude premature labor or emergency cesarean section, as a result of GBS as well. Immunization could help prevent labor complications and infections in mothers and infants.
GBS vaccine might be recommended, once testing is completed, on the same schedule as tetanus toxoid. Tetanus toxoid vaccine is currently recommended for any woman in prenatal care who is not adequately immunized against tetanus.
Unlike the influenza and RSV vaccines, GBS may need to be given only once. "It's possible that one immunization to women of childbearing age could provide protection throughout their reproductive lives," Glezen said. "But this still has to be determined."
He said the vaccine still needs to be tested on pregnant women, in the event that not all women receive the immunization earlier. "Prenatal care will be a very important point of access to delivering the vaccine to women of childbearing age, because that's when we're most likely to see them. We would expect that even if the vaccine is recommended for adolescents, that many women would show up for prenatal care without prior vaccination, so it would be important to know that the vaccine was safe and effective if given during pregnancy."
It has been found that infants born longer than two weeks after maternal immunization have higher antibody titers than infants born within two weeks of maternal immunization. Infants of mothers vaccinated during the third trimester have lower antibody titers than their mothers. Usually 50% to 60% of maternal IgG PRP antibody crosses the placenta after third trimester vaccination. High maternal antibody levels did not suppress infant active antibody response when given PRP conjugated to tetanus toxoid (PRP-T). Upon active immunization, infants born with high maternal antibody titers had responses similar to those whose mothers were not immunized.
Hib vaccines probably will not ever be used on pregnant women in the United States; however, they may be a good way to prevent disease in developing countries. "Even when we had a lot of Hib disease in the United States, most of the Hib disease occurred after 6 months of age," Glezen said. "However, in some developing countries, a lot of the invasive Hib disease occurs before 6 months of age, and it might be difficult to actively immunize those babies before they are exposed."
One-third of all pertussis cases in the United States involve infants younger than 6 months, and these children account for most pertussis-related hospitalizations and deaths and 50% of pneumonia cases. Mothers have proven to be a main source of infant pertussis infection. Maternal cough for seven days or more is an important risk factor. New acellular pertussis vaccines may increase immunity of an infant's older contacts, thus reducing a child's risk of getting the disease. These may be incorporated into the tetanus-diphtheria vaccine.
"This could be given as a booster," Glezen said. If tests prove it to be safe and effective, tetanus-diphtheria and acellular pertussis could be given to pregnant women as well.
For more information:
- Glezen WP, Alpers M. Maternal immunization. Clin Infect Dis 1999;28:219-224.
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