Pregnancy and infectious disease

Definition

Infections in pregnancy may cause maternal illness, fetal birth defects or disorders, postnatal medical concerns, and adverse pregnancy outcomes. Often, maternal symptoms are mild compared with the fetal effects. Infections are spread by vertical transmission, whereby the pregnant woman (or girl) passes an active infection to the fetus in pregnancy through the placenta or through the birth canal during delivery.

The timing of a maternal infection is important. In general, the earlier in pregnancy that a pregnant woman acquires an infection, the less likely the fetus is to acquire the infection through the placenta but the more likely the affected fetus is to have severe symptoms. Conversely, the later in pregnancy that a pregnant woman acquires an infection, the more likely her fetus is to acquire the infection but with less significant abnormal findings. For sexually transmitted diseases, the risk is greatest at time of contact with the vaginal canal during delivery.

After blood tests, urinalyses, or vaginal cultures have confirmed a maternal infection, additional studies of the fetus may be performed. Abnormal ultrasound findings suggest fetal infection but cannot confirm the diagnosis. Invasive prenatal diagnosis by amniocentesis may be available to confirm a fetal infection but cannot detect the severity of the infection. The prognosis, management, and treatment vary depending on the type of infection.

The TORCH Panel

Many infections may be screened using a TORCH (“toxoplasmosis,” “other,” “rubella,” “cytomegalovirus,” and “herpes”) panel. “Other” includes infections such as hepatitis B, syphilis, coxsackie virus, parvovirus, and varicella. The TORCH panel is performed on maternal blood to confirm the presence of either a past or a primary (new) infection in the pregnancy. For many infections, past exposure makes it unlikely that a current pregnancy would be at risk because of maternal immunity.

Congenital toxoplasmosis. Toxoplasmosis is caused by Toxoplasma gondii, a common parasite that typically does not lead to illness in otherwise healthy persons. Those who are at highest risk are those who have outdoor pets (such as cats) who carry the parasite, those who garden, and those who ingest uncooked meat. An infected person may present with fever, fatigue, and sore throat. A primary infection confers an elevated risk of miscarriage or stillbirth, particularly if contracted during the first or second trimester. A third-trimester infection raises the likelihood of the infant being born with congenital toxoplasmosis

Examples of abnormalities found in affected fetuses include calcifications in the brain, water on the brain, and an enlarged or small head size. Newborns have symptoms that range from mild to severe, with little or absent signs of the infection at delivery. They develop inflammation of the retina, leading to visual loss, hearing loss, seizures, cerebral palsy, developmental delay, enlarged liver and spleen, feeding difficulties, and low birth weight. Antibiotics may given to reduce the chance of vertical transmission, although medications are not 100 percent effective.

Congenital rubella (German measles). Most females of childbearing age are immune to rubella because of childhood vaccinations. Pregnant women present with flulike symptoms and arthritis. If a woman acquires the infection within the first sixteen weeks of pregnancy, the risk is greatest (50 to 85 percent) for the fetus to have congenital rubella syndrome, which may entail low birth weight, hearing loss, cataracts, heart defects, enlargement of the spleen, developmental delay, and diabetes. An infection acquired at sixteen to twenty weeks gestation places the pregnancy at a lower risk, and after twenty weeks, an infection does not increase the risk for birth defects. The risks of miscarriage, stillbirth, or prematurity are higher in women who contract rubella. No treatments exist to prevent vertical transmission. The vaccine is recommended before but not during pregnancy.

Congenital cytomegalovirus. Cytomegalovirus is the most common congenital infection in the United States. All pregnant women are susceptible to the infection, although it is more prevalent in populations of low socioeconomic status. A primary infection occurs in 1 to 4 percent of pregnant women and puts the pregnancy at risk for vertical transmission. An infected woman might be asymptomatic or may show mild symptoms that include a fever and muscle aches. Of these women, 30 to 40 percent will transmit the cytomegalovirus to the fetus.

Abnormal ultrasound findings include extra fluid around the fetus or in the fetal tissues, an enlarged heart or heart block, enlarged ventricles of the brain, and calcifications in fetal organs. About 1 in 150 newborns are born with cytomegalovirus. Some newborns have transient symptoms such as jaundice or low birth weight. Others will develop significant long-term complications such as hearing and vision loss, enlargement of liver and spleen, developmental delay, and seizures. Not all findings are readily apparent at delivery. Approximately one-third of severely neurologically affected newborns do not survive.

Treatment for congenital cytomegalovirus is experimental. Initial studies of administering hyperimmunoglobulin to pregnant women are promising, with resolution of abnormal ultrasound findings and delivery of healthy babies. Randomized clinical trials are needed to confirm the efficacy.

Parvovirus. Human parvovirus B19 is a common virus that causes fifth disease (also called erythema infectiosum). Women who work in child care or who have an affected family member are at greatest risk for a primary infection. Many women remain asymptomatic or have mild flulike symptoms. A characteristic red facial rash with a “slapped cheek” appearance is often observed. Risk of miscarriage and stillbirth exists, especially if the infection was acquired and transmitted in the first twenty weeks of pregnancy. There is no increased risk for birth defects, but the fetus is at risk for a heart failure and anemia.

Abnormal ultrasound findings include extra fluid in the fetal tissues, an enlarged heart, and abnormal blood flow in the fetal brain. If the heart infection and anemia are severe enough, they may ultimately result in fetal death. The anemia might require blood transfusions through a percutaneous umbilical blood sampling. The extra fluid may conversely disappear and result in a normal outcome for the pregnancy. No other treatment or vaccines are available.

Sexually Transmitted Diseases

Sexually transmitted diseases (STDs) are routinely screened for at a pregnant woman’s initial prenatal visit. Most STDs are transmitted at delivery by newborn skin contact with secretions in the vaginal canal, although some may cross the placenta. Pregnant women should avoid sexual contact and should take appropriate precautions with partners who are untreated for STDs. Certain STDs are transmitted to the pregnancy through diagnostic procedures such as amniocentesis. Therefore, these procedures may not be recommended. Unlike the foregoing infections, this and the following category include infections that can recur and that require multiple courses of treatment.

Chlamydia. The bacterium Chlamydia trachomatis causes chlamydia infection, the most common bacterial STD in the United States. Seventy-five percent of women are asymptomatic; some have abnormal vaginal bleeding or discharge and pain with sexual intercourse. Antibiotics are prescribed, but when untreated, chlamydia may result in an ectopic pregnancy or a preterm delivery. If there is an untreated chlamydia infection at the time of delivery, vaginal wall contact places the newborn at risk for developing pneumonia and a severe eye infection that could cause eye damage and blindness.

Congenital syphilis. Syphilis is a bacterial infection caused by Treponoma pallidum. Primary syphilis is characterized by an open internal or external genital sore. Without medication, this progresses to secondary and tertiary syphilis with findings of fever, rash, sore throat, hair loss, and, eventually, blindness and dementia. Syphilis may be transmitted through the placenta to the fetus and result in a miscarriage, stillbirth, and premature delivery. Syphilis is also transmitted during both vaginal and cesarean sections, although the latter may reduce infection rates.

Newborns may not show immediate signs of congenital syphilis. Findings include oral and genital sores, rash, jaundice, and anemia. When untreated, children will develop mental retardation, vision and hearing loss, seizures, and bone and teeth damage; death can also occur. If syphilis is diagnosed before the sixteenth week of pregnancy, penicillin is effective in preventing congenital syphilis. After sixteen weeks, treatment is less successful.

Gonorrhea. Gonorrhea is caused by the bacterium Neisseria gonorrhoeae. It is the second most common bacterial STD. One-half of infected women are asymptomatic. Left untreated, it may lead to an ectopic pregnancy, miscarriage, premature delivery, and maternal infection after delivery. The fetal findings include decreased fetal growth. Neonatal effects result from contact with the vaginal wall and include eye or generalized infections and meningitis. Treatment is with antibiotics.

Hepatitis B and C. Newborns have a risk for vertical transmission of either hepatitis B or C, viruses that infect the liver, if a pregnant woman is a chronic carrier of the disease or if she has an acute infection. Risks to the fetus that are transient include jaundice, fatigue, and fever. Long term, a child is at risk for early onset cirrhosis of the liver and liver cancer. For hepatitis B, immunizations are provided in the newborn nursery and are highly effective at preventing infection. A vaccine does not exist for hepatitis C.

Herpes simplex virus. Genital herpes may be caused by either herpes simplex types 1 or 2. The risk to the pregnancy includes a significant eye infection that may result in damage or blindness. The baby is at risk if the woman is having an active outbreak at delivery. In this circumstance, a cesarean section is often performed to avoid neonatal transmission during labor. Maternal infection is treated with oral antibiotics. Women may be on suppression therapy in the third trimester to prevent an outbreak at delivery. Eye drops are routinely administered after birth to prevent a neonatal eye infection.

Human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS). Vertical transmission of HIV may occur during pregnancy or at delivery. Without treatment, the risk to the fetus has been 25 percent. With antiretroviral therapy, the risk has been reduced to 2 percent in developed countries. Certain medications for treating HIV may cause birth defects and disorders, so women are switched to safer medications during pregnancy. A cesarean section may be recommended if the woman has a large amount of virus detected, although this recommendation is controversial.

Zika virus. Zika is a mosquito-borne illness that can be transmitted sexually as well. Zika in otherwise healthy adults typically causes mild flulike symptoms, as well as rash or conjunctivitis, for a period up to a week. Vertical transmission to the fetus can cause microcephaly (small heads and underdeveloped brains). Newborns with congenital Zika syndrome tend to exhibit signs such as partial skull collapse, lower brain mass, eye damage, and restricted body movement due to joint problems and greater-than-average muscle tone. There is no vaccine or specific treatment for Zika. Prevention consists of minimizing exposure to mosquitoes and avoiding unprotected sex with an affected partner for at least six months.

Other Infections

Bacterial vaginosis. Bacterial vaginosis (BV) is an imbalance of the beneficial and harmful vaginal bacteria that leads to an overgrowth of the latter. About 10 to 30 percent of pregnant women are diagnosed with BV, the cause of which is unknown. It is not a sexually transmitted disease, but sexual intercourse does increase the chance of BV. Women with a new partner or multiple sexual partners are at greatest risk. Often women are asymptomatic, but others have a grayish-white discharge with a fishy odor. This may cause a vaginal itch, pain, or a burning sensation. BV is associated with an increased risk for premature labor and delivery, miscarriage, and low birth weight. Treatment includes oral antibiotics. Topical medications alleviate maternal symptoms but do not eliminate pregnancy complications.

Influenza. Influenza is an infection of the respiratory tract. Pregnant women are at increased risk for complications because of a decreased immune response. Symptoms include fever, chills, achy muscles, sore throat, and fatigue. Pregnant women often experience difficulty breathing. The greatest chance of acquiring the flu happens during the winter season (November through March). Data suggest an increased risk for pregnancy loss or premature labor and delivery. An increase in birth defects has not been observed. Maternal deaths have been reported.

Acetaminophen is given for fever control and antiviral medications are prescribed if flulike symptoms are reported. The Centers for Disease Control and Prevention recommends that all pregnant women receive the seasonal and H1N1 flu vaccines. The injected flu vaccine is an inactive form of the virus and does not place the pregnancy at increased risk for either influenza or birth defects. The nasal vaccine is not recommended during pregnancy because it contains live influenza virus.

Listeriosis. The bacterium Listeria monocytogenes causes listeriosis. Although the diagnosis is rare, pregnant women are much more likely to be diagnosed with listeriosis than are other persons.

Listeria may be found in uncooked or undercooked food. Pregnant women should avoid lunch meats, uncooked fish, or refrigerated meats unless these meats are heated to a safe temperature. Also, pregnant women should not consume unpasteurized milk and certain dairy products.

Listeriosis increases the risk of miscarriage, stillbirth, neonatal death, and premature labor. Pregnant women report mild flulike symptoms, including fever, muscle aches, diarrhea, nausea, and vomiting. More severe symptoms appear if the infection spreads to the central nervous system; the severe symptoms include maternal seizures and cognitive disorientation.

Abnormal ultrasound findings include the possibility of an enlarged fetal heart and thickening of the gastrointestinal tract, where the bacteria typically resides. Fetal infection results in death in 20 to 30 percent of cases. Newborns may have significant findings such as breathing difficulties, fever, pneumonia, seizures, rash, jaundice, sepsis, and lethargy. Newborns are at greater risk of meningitis when acquiring the infection through vaginal delivery. Treatment for listeriosis includes antibiotics to prevent vertical transmission and is successful in decreasing the stillbirth and premature delivery rate.

Group B streptococcal infection. Group B Streptococcus (GBS) is a naturally occurring bacterium commonly found in 10 to 30 percent of otherwise healthy women. It lives in either the vagina or the rectum of asymptomatic pregnant women. Women are tested for GBS late in their third trimester of pregnancy by a vaginal or rectal swab. GBS is the most common cause of life-threatening infections of the newborn and is associated with stillbirth. A newborn may develop sepsis, meningitis, or pneumonia. Long-term complications include vision and hearing loss and a risk for neurodevelopmental impairment. Penicillin is given intravenously to women with positive or inconclusive results four hours before delivery to prevent vertical transmission.

Urinary tract infection. Urinary tract infections (UTIs) are very common during pregnancy, with most women remaining asymptomatic. Therefore, urine cultures are performed on all pregnant women. If left untreated, an infection of the kidneys and ureters may occur. Symptoms include fever, back pain, anemia, and nausea and vomiting. Low birth weight and premature delivery result. Treatment is with antibiotics for the current infection and possible prophylactic antibiotics for women with recurrent UTIs.

Chickenpox. A primary maternal varicella infection is associated with the characteristic vesicular rash of chickenpox. More significant complications are maternal bacterial infections, inflammation of the lungs, and central nervous system involvement. During the first and second trimesters, fetal varicella syndrome findings consist of scarred skin, eye defects, underdeveloped limbs, small head size, and developmental delay; however, these findings occur in only less than 2 percent of all fetuses. During the third trimester, the fetus is at risk for severe symptoms and death. Pregnant women with a primary infection are isolated from other pregnant women and infants. Immunoglobulins, which are given when the diagnosis has been confirmed to reduce pregnancy and newborn complications, do not prevent vertical transmission.

Impact

Although many of the aforementioned infectious diseases have either preventive measures or possible treatments in pregnancy, the illnesses remain a significant cause of fetal and maternal morbidity and death. Many of the diagnoses are not detected until after the pregnant woman or the fetus has shown significant symptoms, often when it is too late for effective interventions. Overlapping symptoms also pose difficulties for determining the exact infection.

The impact of a preterm delivery or delivery of a child with multiple medical concerns is felt at the level of the patient and from a public health perspective. Increased long-term care puts a strain on the medical system. Proper patient education, and continuing drug and vaccine development, remain key components of reducing the incidence of infections in pregnancy.

Bibliography

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