Definition
Pregnancy and childbirth present unique challenges to the physiology of
both the pregnant woman and her fetus (or newborn after birth) and significantly
affect the body’s immune system’s ability to combat infection.
The immune system considers a growing fetus to be a foreign object. To
prevent an “attack” by this “object,” the pregnant woman’s immune system
self-modulates, resulting in a condition of immunosuppression that exposes her and
her fetus to infections that would not pose a threat to healthy, nonpregnant women.
In addition, the developing immunity of the fetus does not effectively protect against
disease. Maternal IgG antibodies (proteins that fight infection, also called
immunoglobulins) cross the placenta to provide protection, but IgM (immunoglobulin
M) antibodies do not. The function of disease-fighting white blood cells and
complement-protein activity (another form of immune protection) are decreased.
Threats to the fetus include bacterial, viral, and other pathogens
inside and outside the genital tract. Some of these cause serious infection in
both the pregnant woman and the fetus, while others threaten only the pregnant
women or only the fetus. Modes of transmission vary too.
Congenital infections, which occur during pregnancy, cross the placenta to
infect a growing fetus and may result in abnormal development, fetal disease, or
fetal death. These include the TORCH agents, an acronym that has been used to
describe the most common congenital infections. Intrapartum infections are passed during labor and delivery as the
fetus travels through the infected birth canal. Examples of these infections
include many of the sexually transmitted diseases (STDs)
and group B Streptococcus. Postpartum infections occur after
delivery and most often involve the genitourinary tract of the mother. In the
past, these infections were known as childbirth fever and were once leading causes
of morbidity and mortality. However, with the widespread use of improved sterile
techniques and of antibiotics, incidence has decreased dramatically. In
addition, some microbes (such as human immunodeficiency virus and
cytomegalovirus) can infect the newborn through
breast-feeding; other infections are acquired during the postdelivery hospital
stay, an infection known as nosocomial.
Threats to the Fetus and the Newborn
Many infectious agents are able to cross the placenta during pregnancy and cause congenital infection, whether these agents originate in the genitourinary system or elsewhere in the body. Some organisms that cause little or no clinical illness in the pregnant woman can present significant danger to the developing fetus; these organisms are teratogenic (they cause birth defects). In utero transmission of infection can occur at any time before birth, and the period of greatest risk varies by organism. TORCH is the acronym that has been used for these common organisms in the past, but as more and more organisms belonging to the “other” category are identified, the term has lost favor. The original purpose of the TORCH designation was to group infections with similar patterns of transmission and presentation. TORCH includes Toxoplasma, coxsackie virus, human parvovirus, hepatitis B, syphilis, Epstein-Barr virus, varicella zoster virus (or chickenpox; a primary infection during pregnancy is considered a medical emergency), LCMV (lymphocytic choriomeningitis), parvovirus B19, rubella virus, cytomegalovirus (CMV), HIV, and herpes simplex virus.
The agents responsible for congenital infection carry significant risk of morbidity and mortality and can cause neurological damage, blindness, deafness, cardiac defects, intrauterine growth restriction, skin lesions, and a host of other abnormalities. HIV, one of the congenital agents recently added to the foregoing list, is now known to be a major cause of infant mortality worldwide. Influenza, including H1N1 (swine flu), is a growing significant threat. Many of these organisms can also be transmitted during passage through the birth canal if they are present at the time of delivery.
Routine maternal screening for serologic evidence of organisms causing congenital infection during pregnancy is commonplace in many parts of the world, but its use as a diagnostic tool is controversial in the United States because of overuse and a lack of consistent interpretation of results. Screening is limited to cases in which exposure is known or suspected or in which symptoms are present. (Syphilis is a notable exception, and it is routinely screened for.)
Symptoms of infection in the newborn cover a broad range and are often nonspecific. Fever, hypothermia, vomiting, rash, and decreased muscle tone may indicate infectious illness, and many congenital infections acquired during gestation are accompanied by abnormalities specific to the organism involved. When a diagnosis is confirmed, the organism identified determines the availability of treatment for mother and newborn. Antiviral medications, intravenous gammaglobulin (IVIg), and antibiotics are mainstays of treatment.
Listeriosis is a less common but devastating cause of fetal infection. Maternal
infection comes from eating contaminated food. The organism crosses the placenta
to cause amnionitis (infection of the amniotic sac); the infant mortality rate for
this infection is almost 50 percent. Prevention through avoidance of high-risk
foods is the mainstay treatment, but infection can sometimes be treated with
antibiotics (with limited success).
The most common cause of life-threatening infection in the newborn is group B Streptococcus (GBS), which affects both mother and child. GBS is a beta-hemolytic gram-positive coccus that is often found in normal vaginal flora. Intrapartum transmission to the newborn occurs during delivery and can be the result of ascending infection after the rupture of membranes or of direct contact in the vaginal canal. Infection can cause severe illness and death.
Infants with GBS infection will present with either early-onset or late-onset disease, depending on the time between delivery and onset of symptoms. Early-onset disease occurs before seven days of age and includes symptoms of sepsis, pneumonia, or meningitis. Newborns who become ill between age seven and eighty-nine days have late-onset disease, which typically manifests as generalized bacteremia and meningitis. Common sequelae for those who survive the infection are vision loss, neurologic damage, and developmental delay.
Up to 30 percent of pregnant girls and women are colonized with GBS, but less
than 1 percent of these cases have symptoms of disease. Therefore, the
Centers for
Disease Control and Prevention (CDC) recommends GBS screening
by vaginal and rectal cultures for all pregnant females who are between
thirty-five and thirty-seven weeks gestation. New mothers with positive or unknown
culture results are treated with antibiotic prophylaxis (most often with
penicillin G), and their newborns are closely observed for signs and symptoms of
disease. The incidence of early-onset disease has decreased dramatically since
screening and prophylaxis became routine, but the frequency of late-onset disease
remains stable.
Other causes of intrapartum disease transmission include sexually transmitted
organisms such as chlamydia and gonorrhea, so the CDC recommends
routine screening of all women early in pregnancy. Antibiotic treatment can
prevent infant disease. Bacteria colonizing the vagina and rectum of the pregnant
woman, bacteria including gram-positives, gram-negatives, aerobes, and anaerobes,
can overgrow and cause infection of the fetus or newborn; these bacteria can also
cause preterm labor and delivery. The index of suspicion required to seek
diagnosis and treatment should be low.
The degree of risk associated with congenital, intrapartum, and postpartum infections in the newborn is highly correlated with gestational age. The immune function of premature infants is less mature than that of term infants, with decreased white-cell function, antibody production, and complement activity. Premature infants spend more time in the hospital and undergo invasive procedures, exposing them to nosocomial (hospital acquired) infection.
Threats During and After Pregnancy
In spite of the immune suppression that is a hallmark of forty weeks of pregnancy, the most serious infectious disease dangers for the pregnant woman-mother are from intrapartum and postpartum events (during and immediately following birth). Historically, childbirth fever from genital tract infection following delivery has been a leading cause of maternal morbidity and mortality. The traumatic nature of vaginal or cesarean delivery predisposes to the local spread of colonized bacteria, and though the incidence has decreased significantly with the widespread use of improved hygiene and of antibiotics, obstetric infection still accounts for more than 12 percent of maternal deaths.
Puerperal or postpartum infection is a bacterial
infection that occurs during or after childbirth. Most of
these infections begin in the genitourinary tract and infect the uterus and
surrounding areas soon after delivery. In some cases, however, organisms may be
carried through the blood to seed other parts of the body or may occur through
breast-feeding. Vaginal delivery carries an infection risk of 1 to 3 percent,
while the risk after cesarean delivery may be as high as 20 percent. Other factors making
infection more likely include repeated vaginal examinations during labor, early
rupture of membranes and early internal fetal monitoring, postpartum hemorrhage,
retained placental fragments, prolonged labor, young age, and low socioeconomic
group.
Postpartum infection is typically diagnosed when a fever greater than 100.4°
Fahrenheit (38° Celsius) is present for two of ten days following delivery. Endometritis (infection of the uterine lining) is the most
common site, followed by postcesarean wound infections, perineal cellulitis
(infection of perineal tissue), mastitis (breast infection), urinary tract infections (UTIs), and septic phlebitis
(infection of pelvic blood clots). Maternal death rates because of infection are
approximately 0.6 deaths per 100,000 live births.
Symptoms may include fever, low abdominal and uterine pain, heavy malodorous lochia (bloody discharge that follows delivery), chills, and general malaise. Those with a UTI may have pain on voiding and nausea and vomiting. Those who received general anesthesia for cesarean delivery may present with symptoms of pneumonia, and wound infections may develop swelling and drainage. Breast infection, which can occur when nipples become sore and cracked, allowing bacteria to enter, manifests as a breast that appears red, warm, swollen, and painful (often after the immediate postpartum period but before six weeks after delivery).
Diagnosis is based on observation of symptoms, physical examination, and the
results of bacterial cultures and blood studies. If left untreated, severe
complications of postpartum infection can occur and include peritonitis
(infection of the abdominal lining), septic embolism (infected blood clots that
travel to lungs and other areas of the body), and septic shock.
Treatment generally includes intravenous antibiotics for forty-eight hours or
more, sometimes followed by a course of oral medication after hospital
discharge.
Colonization with group B Streptococcus during pregnancy is a cause of maternal UTI, amnionitis, endometritis, and fetal loss. Rarely, it can cause pelvic abscess, meningitis, and endocarditis. Clinical diagnosis of infection is difficult because few pregnant women who carry GBS develop signs and symptoms of disease. The current screening and treatment approach, which is delayed until thirty-five to thirty-seven weeks gestation, just before delivery, does not address the incidence of maternal GBS disease during pregnancy. Several vaccines to prevent GBS colonization and disease are in development; routine vaccination would decrease risk significantly.
UTI is a common problem for women, and the risk is exacerbated during pregnancy. The proximity of the (short) urethra to the vagina and anus, compounded by (in the pregnant woman) a weakened immune system and by stasis caused by a growing fetus crowding the urinary system, make frequent UTIs a common complaint. Responsible organisms include Escherichia coli, Klebsiella, Enterobacter, Enterococcus, GBS, staph species, and Proteus.
Infection may be symptomatic or asymptomatic, and both are clinically important
to the health of the mother and newborn. Asymptomatic infection is more likely to
lead to acute pyelonephritis (kidney infection), which is a common reason
for hospitalization in pregnant women. The severity of infection varies, but it
can progress to generalized urosepsis and is associated with low neonatal birth
weight and prematurity. Because so many of these infections are asymptomatic, it
is recommended that all pregnant women be screened by urine culture during early
pregnancy and treated with antibiotics if indicated.
Bacterial
vaginosis is a condition caused by the overgrowth of
colonizing bacteria of the vagina. Normal vaginal flora varies depending on the pH
of the vagina, and overgrowth is polymicrobial. It may be asymptomatic or may
present with burning and discharge. The organisms can ascend and infect the
amniotic membranes, causing premature labor. It is estimated that 40 percent of
these pregnancies will go on to have preterm labor. Therefore, the CDC recommends
that females at risk for premature labor (prior preterm delivery or high-risk
pregnancy) be screened for bacterial vaginosis and treated if indicated.
All antimicrobial medications cross the placenta and expose the fetus to
possible adverse effects, so they should be used with caution. Most commonly
prescribed antibiotics are safe for use during pregnancy and include
penicillins, cephalosporins, nitrofurantoin, and macrolides,
but some have been associated with birth defects and disorders (tetracyclines) and increased toxicity (sulfonamides).
Impact
Infections associated with childbirth affect pregnant girls and women and their
fetuses and newborns worldwide. Infections can occur from the time the fertilized
egg is implanted up to and beyond the moment of delivery, sometimes with
devastating results. Expanded prenatal care, improved hygiene, aseptic
technique, and the use of antibiotics have made death from
childbed fever rare in the developed world, but congenital and perinatal
infections continue to take a toll, especially in developing countries.
Infection is understood to be a major cause of preterm birth and may account for 25 to 40 percent of events that result in maternal and fetal (and newborn) morbidity and mortality; infections also add to the rapidly rising cost of health care. The development of vaccines to protect newborns and mothers from disease is ongoing.
Bibliography
Campos, Bonnie C., and Jennifer Brown. Protect Your Pregnancy. New York: McGraw-Hill, 2003. A pregnancy guide with a special focus on at-risk pregnancies. Reviews how to recognize signs and symptoms of pregnancy complications and explores preexisting and developing medical conditions that can lead to premature delivery, among other topics.
Cunningham, F. Gary, et al. Williams Obstetrics. 23d ed. New York: McGraw-Hill, 2010. The bible of obstetrics theory and practice.
Forsgren, M. “Prevention of Congenital and Perinatal Infections.” Eurosurveillance 14 (2009). Available at http://www.eurosurveillance.org/viewarticle.aspx?articleid=19131. A scholarly look at what can be done to prevent infection, now and in the future.
Newell, Marie-Louise, and James McIntyre. Congenital and Perinatal Infections: Prevention, Diagnosis, and Treatment. New York: Cambridge University Press, 2000. A comprehensive examination of infections associated with childbirth for medical professionals and educated general readers.
Thornton, C. A. “Immunology of Pregnancy.” Proceedings of the Nutrition Society 69 (2010): 357-365. An advanced article on the significance of maternal diet and nutrition in healthy fetal development.
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