Childbirth and infectious disease

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 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 also vary.

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 post-delivery 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 gamma globulin (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.

In 2024, the Centers for Disease Control and Prevention (CDC) reported that around 25 percent of pregnant women carry GBS, but testing is important because most women do not show symptoms of the disease. Therefore, the 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

Despite 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 the mother and child to colonized bacteria, and though the incidence has decreased significantly with the widespread use of improved hygiene and of antibiotics, obstetric infection in 2022 was still concerning for the WHO and CDC. Globally, eleven out of every thousand women experienced life-threatening infections during or after birth. Though this percentage in the United States and other developed nations remained much lower than that of developing nations, 33 out of every 100,000 births in the US were impacted by infections in 2022. The use of antibiotics after birth, particularly following the use of episiotomy, forceps, and primiparity, is critical in preventing infection. The American Journal of Obstetrics and Gynecology published a study in 2023 noting that each 15-minute interval between the administration of antibiotics and birth increased the risk of infection by 3 percent.

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. A 2020 study found that, among the 7.17 million births surveyed, cesarean delivery carried a 13 percent higher risk for infection-related hospitalization. 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° F (38° C) is present for two of ten days following delivery. Endometritis (infection of the uterine lining) is the most common site, followed by post-cesarean wound infections, perineal cellulitis (infection of perineal tissue), mastitis (breast infection), urinary tract infections (UTIs), and septic phlebitis (infection of pelvic blood clots).

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. Nearly 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 prescribed antibiotics are safe for use during pregnancy and include penicillin, 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.

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